Brain aromatase: roles in reproduction and neuroprotection.

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Roselli, Charles F

2007-01-01

It is well established that aromatization constitutes an essential part of testosterone's signaling pathway in brain and that estrogen metabolites, often together with testosterone, organize and activate masculine neural circuits. This paper summarizes the current understanding regarding the distribution, regulation and function of brain aromatase in mammals. Data from our laboratory are presented that highlight the important function of aromatase in the regulation of androgen feedback sensitivity in non-human primates and the possible role that aromatase plays in determining the brain structure and sexual partner preferences of rams. In addition, new data is presented indicating that the capacity for aromatization in cortical astrocytes is associated with cell survival and may be important for neuroprotection. It is anticipated that a better appreciation of the physiological and pathophysiological functions of aromatase will lead to important clinical insights.

Organizing effects of sex steroids on brain aromatase activity in quail.

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Charlotte A Cornil

2011-04-01

Full Text Available Preoptic/hypothalamic aromatase activity (AA is sexually differentiated in birds and mammals but the mechanisms controlling this sex difference remain unclear. We determined here (1 brain sites where AA is sexually differentiated and (2 whether this sex difference results from organizing effects of estrogens during ontogeny or activating effects of testosterone in adulthood. In the first experiment we measured AA in brain regions micropunched in adult male and female Japanese quail utilizing the novel strategy of basing the microdissections on the distribution of aromatase-immunoreactive cells. The largest sex difference was found in the medial bed nucleus of the stria terminalis (mBST followed by the medial preoptic nucleus (POM and the tuberal hypothalamic region. A second experiment tested the effect of embryonic treatments known to sex-reverse male copulatory behavior (i.e., estradiol benzoate [EB] or the aromatase inhibitor, Vorozole on brain AA in gonadectomized adult males and females chronically treated as adults with testosterone. Embryonic EB demasculinized male copulatory behavior, while vorozole blocked demasculinization of behavior in females as previously demonstrated in birds. Interestingly, these treatments did not affect a measure of appetitive sexual behavior. In parallel, embryonic vorozole increased, while EB decreased AA in pooled POM and mBST, but the same effect was observed in both sexes. Together, these data indicate that the early action of estrogens demasculinizes AA. However, this organizational action of estrogens on AA does not explain the behavioral sex difference in copulatory behavior since AA is similar in testosterone-treated males and females that were or were not exposed to embryonic treatments with estrogens.

Aromatase in the brain: not just for reproduction anymore.

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Garcia-Segura, L M

2008-06-01

Aromatase, the enzyme that synthesises oestrogens from androgen precursors, is expressed in the brain, where it has been classically associated with the regulation of neuroendocrine events and behaviours linked with reproduction. Recent findings, however, have revealed new unexpected roles for brain aromatase, indicating that the enzyme regulates synaptic activity, synaptic plasticity, neurogenesis and the response of neural tissue to injury, and may contribute to control nonreproductive behaviours, mood and cognition. Therefore, the function of brain aromatase is not restricted to the regulation of reproduction as previously thought.

Are separable aromatase systems involved in hormonal regulation of the male brain

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Hutchison, J.B.; Schumacher, M.; Steimer, T.; Gahr, M.

1990-01-01

In vitro study of testosterone (T) metabolism shows that formation of estradiol-17 beta (E2) is regionally specific within the preoptic area (POA) of the male ring dove. The POA is known to be involved in the formation of E2 required for specific components of male sexual behavior. Two sub-areas of high aromatase activity, anterior (aPOA) and posterior preoptic (pPOA) areas, have been identified. Aromatase activity is higher in aPOA than in pPOA. The aromatase activity within the aPOA is also more sensitive to the inductive effects of low circulating T, derived from subcutaneous silastic implants, than the enzyme activity in pPOA. Kinetic analysis of preoptic fractions indicates that a similar high-affinity enzyme occurs in both areas (apparent Km less than 14 nM), but the Vmax of aPOA enzyme activity is higher than pPOA. Cells containing estrogen receptors (ER) are localized in areas of high aromatase activity. There is overlap between immunostained cells in the aPOA and in samples containing inducible aromatase activity measured in vitro. Within the aPOA there is a higher density of ER cells in the nucleus preopticus medialis. The pPOA area also contains ER, notably in the nucleus interstitialis, but at a lower density. We conclude that the hormonal regulation of the male preoptic-anterior hypothalamic region, which is a target for the behavioral action of T, involves at least two inducible aromatase systems with associated estrogen receptor cells

Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.

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Alejandra Perez-Sepulveda

Full Text Available Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE.Serum samples were collected at 32-36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16 and pregnant controls (n = 32. The effect of oxygen tension on placental cells was assessed by incubation JEG-3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6 were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels. Aromatase content and estrogens and androgens concentrations were measured.The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG-3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic

Effects of testosterone and its metabolites on aromatase-immunoreactive cells in the quail brain: relationship with the activation of male reproductive behavior.

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Balthazart, J; Foidart, A; Absil, P; Harada, N

1996-01-01

The enzyme aromatase converts testosterone (T) into 17 beta-estradiol and plays a pivotal role in the control of reproduction. In particular, the aromatase activity (AA) located in the preoptic area (POA) of male Japanese quail is a limiting step in the activation by T of copulatory behavior. Aromatase-immunoreactive (ARO-ir) cells of the POA are specifically localized within the cytoarchitectonic boundaries of the medial preoptic nucleus(POM), a sexually dimorphic and steroid-sensitive structure that is a necessary and sufficient site of steroid action in the activation of behavior. Stereotaxic implantation of aromatase inhibitors in but not around the POM strongly decreases the behavioral effects of a systemic treatment with T of castrated males. AA is decreased by castration and increased by aromatizable androgens and by estrogens. These changes have been independently documented at three levels of analysis: the enzymatic activity measured by radioenzymatic assays in vitro, the enzyme concentration evaluated semi-quantitatively by immunocytochemistry and the concentration of its messenger RNA quantified by reverse transcription-polymerase chain reaction (RT-PCR). These studies demonstrate that T acting mostly through its estrogenic metabolites regulates brain aromatase by acting essentially at the transcriptional level. Estrogens produced by central aromatization of T therefore have two independent roles: they activate male copulatory behavior and they regulate the synthesis of aromatase. Double label immunocytochemical studies demonstrate that estrogen receptors(ER) are found in all brain areas containing ARO-ir cells but the extent to which these markers are colocalized varies from one brain region to the other. More than 70% of ARO-ir cells contain detectable ER in the tuberal hypothalamus but less than 20% of the cells display this colocalization in the POA. This absence of ER in ARO-ir cells is also observed in the POA of the rat brain. This suggests that

The sex-specific associations of the aromatase gene with Alzheimer's disease and its interaction with IL10 in the Epistasis Project.

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Medway, Christopher; Combarros, Onofre; Cortina-Borja, Mario; Butler, Helen T; Ibrahim-Verbaas, Carla A; de Bruijn, Renée F A G; Koudstaal, Peter J; van Duijn, Cornelia M; Ikram, M Arfan; Mateo, Ignacio; Sánchez-Juan, Pascual; Lehmann, Michael G; Heun, Reinhard; Kölsch, Heike; Deloukas, Panos; Hammond, Naomi; Coto, Eliecer; Alvarez, Victoria; Kehoe, Patrick G; Barber, Rachel; Wilcock, Gordon K; Brown, Kristelle; Belbin, Olivia; Warden, Donald R; Smith, A David; Morgan, Kevin; Lehmann, Donald J

2014-02-01

Epistasis between interleukin-10 (IL10) and aromatase gene polymorphisms has previously been reported to modify the risk of Alzheimer's disease (AD). However, although the main effects of aromatase variants suggest a sex-specific effect in AD, there has been insufficient power to detect sex-specific epistasis between these genes to date. Here we used the cohort of 1757 AD patients and 6294 controls in the Epistasis Project. We replicated the previously reported main effects of aromatase polymorphisms in AD risk in women, for example, adjusted odds ratio of disease for rs1065778 GG=1.22 (95% confidence interval: 1.01-1.48, P=0.03). We also confirmed a reported epistatic interaction between IL10 rs1800896 and aromatase (CYP19A1) rs1062033, again only in women: adjusted synergy factor=1.94 (1.16-3.25, 0.01). Aromatase, a rate-limiting enzyme in the synthesis of estrogens, is expressed in AD-relevant brain regions ,and is downregulated during the disease. IL-10 is an anti-inflammatory cytokine. Given that estrogens have neuroprotective and anti-inflammatory activities and regulate microglial cytokine production, epistasis is biologically plausible. Diminishing serum estrogen in postmenopausal women, coupled with suboptimal brain estrogen synthesis, may contribute to the inflammatory state, that is a pathological hallmark of AD.

Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels

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Nicolas Defarge

2016-02-01

Full Text Available Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH, the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18–2000 times for co-formulants, 8–141 times for formulations, and not the declared active ingredient glyphosate (G alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.

Effects of Pharmaceuticals Used for Breast Cancer Treatment on Reproduction and Aromatase Activity in a Marine Fish

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Laboratory experiments were conducted with the marine fish cunner (Tautogolabrus adspersus) to evaluate whether four pharmaceuticals used in breast cancer treatment have an impact on reproduction or aromatase activity. Tamoxifen binds to estrogen receptors, while anastrozole, let...

Aromatase inhibitor treatment limits progression of peritoneal endometriosis in baboons.

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Langoi, David; Pavone, Mary Ellen; Gurates, Bilgin; Chai, Daniel; Fazleabas, Asgerally; Bulun, Serdar E

2013-03-01

To determine the effect of inhibiting aromatase activity on endometrial lesion growth and aromatase expression in a baboon model of induced endometriosis. Prospective study. Primate research institute. Sixteen olive baboons. Sixteen olive baboons with induced endometriosis were examined with laparoscopy 10 months after disease inoculation. Animals in group 1 (n = 10) were treated with 1.25 mg/d of the aromatase inhibitor (AI) letrozole, and animals in group 2 (n = 6) were given a placebo for a total of 6 months. Total number of endometriotic lesions, morphology, and volume of lesions, as well as semiquantitative reverse transcription-polymerase chain reaction and quantitative polymerase chain reaction for levels of aromatase cytochrome messenger RNA were measured. Ovarian volumes were evaluated before treatment initiation and every 2 months during the study. Treatment of group 1 animals with an AI significantly decreased lesion volume from baseline measurements, whereas the placebo-treated animals showed an increase in lesion volume. Aromatase messenger RNA levels in lesions in the AI-treated animals were significantly lower compared with the placebo-treated animals. Ovarian volumes were significantly increased at 6 months of AI treatment compared with pretreatment volumes. These findings suggest that suppression of aromatase cytochrome P450 may inhibit the in vivo growth of endometriotic lesions in baboons. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination

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Benachour, Nora; Moslemi, Safa; Sipahutar, Herbert; Seralini, Gilles-Eric

2007-01-01

Xenobiotics may cause long-term adverse effects in humans, especially at the embryonic level, raising questions about their levels of exposure, combined effects, and crucial endpoints. We are interested in the possible interactions between xenobiotic endocrine disrupters, cellular viability and androgen metabolism. Accordingly, we tested aroclor 1254 (A1254), atrazine (AZ), o,p'-DDT, vinclozolin (VZ), p,p'-DDE, bisphenol A (BPA), chlordecone (CD), nonylphenol (NP), tributylin oxide (TBTO), and diethylstilbestrol (DES) for cellular toxicity against human embryonic 293 cells, and activity against cellular aromatase, but also on placental microsomes and on the purified equine enzyme. Cellular viability was affected in 24 h by all the xenobiotics with a threshold at 50 μM (except for TBTO and DES, 10 μM threshold), and aromatase was inhibited at non-toxic doses. In combination synergism was observed reducing the threshold values of toxicity to 4-10 μM, and aromatase activity by 50% in some cases. In placental microsomes the most active xenobiotics rapidly inhibited microsomal aromatase in a manner independent of NADPH metabolism. Prolonged exposures to low doses in cells generally amplified by 50 times aromatase inhibition. These xenobiotics may act by inhibition of the active site or by allosteric effects on the enzyme. Bioaccumulation is a feature of some xenobiotics, especially chlordecone, DDT and DDE, and low level chronic exposures can also affect cell signaling mechanisms. This new information about the mechanism of action of these xenobiotics will assist in improved molecular design with a view to providing safer compounds for use in the (human) environment

Modulation of Aromatase Activity as a Mode of Action for Endocrine Disrupting Chemicals in a Marine Fish

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The steroidogenic enzyme aromatase catalyzes the conversion of androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) and therefore plays a central role in reproduction. In contrast to most vertebrates, teleost fish have two distinct forms of aromatase....

Inhibitory effect of luteolin on estrogen biosynthesis in human ovarian granulosa cells by suppression of aromatase (CYP19).

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Lu, Dan-feng; Yang, Li-juan; Wang, Fei; Zhang, Guo-lin

2012-08-29

Inhibition of aromatase, the key enzyme in estrogen biosynthesis, is an important strategy in the treatment of breast cancer. Several dietary flavonoids show aromatase inhibitory activity, but their tissue specificity and mechanism remain unclear. This study found that the dietary flavonoid luteolin potently inhibited estrogen biosynthesis in a dose- and time-dependent manner in KGN cells derived from human ovarian granulosa cells, the major source of estrogens in premenopausal women. Luteolin decreased aromatase mRNA and protein expression in KGN cells. Luteolin also promoted aromatase protein degradation and inhibited estrogen biosynthesis in aromatase-expressing HEK293A cells, but had no effect on recombinant expressed aromatase. Estrogen biosynthesis in KGN cells was inhibited with differing potencies by extracts of onion and bird chili and by four other dietary flavonoids: kaempferol, quercetin, myricetin, and isorhamnetin. The present study suggests that luteolin inhibits estrogen biosynthesis by decreasing aromatase expression and destabilizing aromatase protein, and it warrants further investigation as a potential treatment for estrogen-dependent cancers.

Synthesis of Triphenylethylene Bisphenols as Aromatase Inhibitors That Also Modulate Estrogen Receptors.

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Lv, Wei; Liu, Jinzhong; Skaar, Todd C; O'Neill, Elizaveta; Yu, Ge; Flockhart, David A; Cushman, Mark

2016-01-14

A series of triphenylethylene bisphenol analogues of the selective estrogen receptor modulator (SERM) tamoxifen were synthesized and evaluated for their abilities to inhibit aromatase, bind to estrogen receptor α (ER-α) and estrogen receptor β (ER-β), and antagonize the activity of β-estradiol in MCF-7 human breast cancer cells. The long-range goal has been to create dual aromatase inhibitor (AI)/selective estrogen receptor modulators (SERMs). The hypothesis is that in normal tissue the estrogenic SERM activity of a dual AI/SERM could attenuate the undesired effects stemming from global estrogen depletion caused by the AI activity of a dual AI/SERM, while in breast cancer tissue the antiestrogenic SERM activity of a dual AI/SERM could act synergistically with AI activity to enhance the antiproliferative effect. The potent aromatase inhibitory activities and high ER-α and ER-β binding affinities of several of the resulting analogues, together with the facts that they antagonize β-estradiol in a functional assay in MCF-7 human breast cancer cells and they have no E/Z isomers, support their further development in order to obtain dual AI/SERM agents for breast cancer treatment.

Aromatase inhibitors in men: effects and therapeutic options

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de Jong Frank H

2011-06-01

Full Text Available Abstract Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty. Long-term efficacy and safety of the use of aromatase inhibitors has not yet been established in males, however, and their routine use is therefore not yet recommended.

Aromatase expression is increased in BRCA1 mutation carriers

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Chand, Ashwini L; KConFab; Simpson, Evan R; Clyne, Colin D

2009-01-01

Until recently, the molecular mechanisms explaining increased incidence of ovarian and breast cancers in carriers of BRCA1 gene mutations had not been clearly understood. Of significance is the finding that BRCA1 negatively regulates aromatase expression in vitro. Our objective was to characterise aromatase gene (CYP19A1) and its promoter expression in breast adipose and ovarian tissue in BRCA1 mutation carriers and unaffected controls. We measured aromatase transcripts, total and promoter-specific (PII, PI.3, PI.4) in prophylactic oophorectomy or mastectomy, therapeutic mastectomy, ovarian and breast tissue from unaffected women. We demonstrate that the lack of functional BRCA1 protein correlates to higher aromatase levels in 85% of BRCA1 mutation carriers. This increase is mediated by aberrant transcriptional regulation of aromatase; in breast adipose by increases in promoter II/I.3 and I.4-specific transcripts; and in the ovary with elevation in promoter I.3 and II-specific transcripts. Understanding the link between BRCA1 and aromatase is significant in terms of understanding why carcinogenesis is restricted to estrogen-producing tissues in BRCA1 mutation carriers

Evidence for an Elevated Aspartate pKa in the Active Site of Human Aromatase*

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Di Nardo, Giovanna; Breitner, Maximilian; Bandino, Andrea; Ghosh, Debashis; Jennings, Gareth K.; Hackett, John C.; Gilardi, Gianfranco

2015-01-01

Aromatase (CYP19A1), the enzyme that converts androgens to estrogens, is of significant mechanistic and therapeutic interest. Crystal structures and computational studies of this enzyme shed light on the critical role of Asp309 in substrate binding and catalysis. These studies predicted an elevated pKa for Asp309 and proposed that protonation of this residue was required for function. In this study, UV-visible absorption, circular dichroism, resonance Raman spectroscopy, and enzyme kinetics were used to study the impact of pH on aromatase structure and androstenedione binding. Spectroscopic studies demonstrate that androstenedione binding is pH-dependent, whereas, in contrast, the D309N mutant retains its ability to bind to androstenedione across the entire pH range studied. Neither pH nor mutation perturbed the secondary structure or heme environment. The origin of the observed pH dependence was further narrowed to the protonation equilibria of Asp309 with a parallel set of spectroscopic studies using exemestane and anastrozole. Because exemestane interacts with Asp309 based on its co-crystal structure with the enzyme, its binding is pH-dependent. Aromatase binding to anastrozole is pH-independent, consistent with the hypothesis that this ligand exploits a distinct set of interactions in the active site. In summary, we assign the apparent pKa of 8.2 observed for androstenedione binding to the side chain of Asp309. To our knowledge, this work represents the first experimental assignment of a pKa value to a residue in a cytochrome P450. This value is in agreement with theoretical calculations (7.7–8.1) despite the reliance of the computational methods on the conformational snapshots provided by crystal structures. PMID:25425647

Potential effect of Olea europea leaves, Sonchus oleraceus leaves and Mangifera indica peel extracts on aromatase activity in human placental microsomes and CYP19A1 expression in MCF-7 cell line: Comparative study.

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Shaban, N Z; Hegazy, W A; Abdel-Rahman, S M; Awed, O M; Khalil, S A

2016-08-29

Aromatase inhibitors (AIs) provide novel approaches to the adjuvant therapy for postmenopausal women with estrogen-receptor-positive (ER+) breast cancers. In this study, different plant extracts from Olea europaea leaves (OLE), Sonchus oleraceus L. (SOE) and Mangifera indica peels (MPE) were prepared to identify phytoconstituents and measure antioxidant capacities. The effects of these three extracts on aromatase activity in human placental microsomes were evaluated. Additionally, the effects of these extracts on tissue-specific promoter expression of CYP19A1 gene in cell culture model (MCF-7) were assessed using qRT-PCR. Results showed a concentration-dependent decrease in aromatase activity after treatment with OLE and MPE, whereas, SOE showed a biphasic effect. The differential effects of OLE, SOE and MPE on aromatase expression showed that OLE seems to be the most potent suppressor followed by SOE and then MPE. These findings indicate that OLE has effective inhibitory action on aromatase at both the enzymatic and expression levels, in addition to its cytotoxic effect against MCF-7 cells. Also, MPE may be has the potential to be used as a tissue-specific aromatase inhibitor (selective aromatase inhibitor) and it may be promising to develop a new therapeutic agent against ER+ breast cancer.

Aromatase inhibitor (anastrozole) affects growth of endometrioma cells in culture.

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Badawy, Shawky Z A; Brown, Shereene; Kaufman, Lydia; Wojtowycz, Martha A

2015-05-01

To study the effects of aromatase inhibitor (anastrozole) on the growth and estradiol secretion of endometrioma cells in culture. Endometrioma cells are grown in vitro until maximum growth before used in this study. This was done in the research laboratory for tissue culture, in an academic hospital. Testosterone at a concentration of 10 μg/mL was added as a substrate for the intracellular aromatase. In addition, aromatase inhibitor was added at a concentration of 200 and 300 μg/mL. The effect on cell growth and estradiol secretion is evaluated using Student's t-test. The use of testosterone increased estradiol secretion by endometrioma cells in culture. The use of aromatase inhibitor significantly inhibited the growth of endometrioma cells, and estradiol secretion. Aromatase inhibitor (anastrozole) may be an effective treatment for endometriosis due to inhibition of cellular aromatase. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

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Saldanha Colin J

2011-07-01

Full Text Available Abstract Background Estrogens from peripheral sources as well as central aromatization are neuroprotective in the vertebrate brain. Under normal conditions, aromatase is only expressed in neurons, however following anoxic/ischemic or mechanical brain injury; aromatase is also found in astroglia. This increased glial aromatization and the consequent estrogen synthesis is neuroprotective and may promote neuronal survival and repair. While the effects of estradiol on neuroprotection are well studied, what induces glial aromatase expression remains unknown. Methods Adult male zebra finches (Taeniopygia guttata were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohisotchemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA, an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test. Results Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression. Conclusions These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.

Purification of human placental aromatase cytochrome P-450 with monoclonal antibody and its characterization

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Yoshida, Nobutaka; Osawa, Yoshio

1991-01-01

A simple and efficient method is described for the purification of microsomal aromatase cytochrome P-450 from human placenta. The enzyme was solubilized with Emulgen 913 and sodium cholate and subjected to chromatography on a column of Sepharose 4B couples with a specific monoclonal antibody, followed by hydroxyapatite column chromatography. The specific cytochrome P-450 content of purified aromatase was 13.1 (12-14.8) nmol/mg of protein. Aromatase assays were carried out with reconstituted systems of bovine liver P-450 reductase and dilauroyl-L-α-phosphatidylcholine with [1β- 3 H,4- 14 C]androstenedione as substrate. The total recovery of purified aromatase activity was 32.2%, and P-450 recovery was 17.6%. The very high K m value for 16α-hydroxytestosterone aromatization gives a reasonable indication that estriol is not the directly aromatized product in the fetoplacental unit of human pregnancy. The aromatase P-450 was subjected to SDS-polyacrylamide gel electrophoresis in increasing quantities. Silver stain detection techniques indicated a single band having a molecular mass of 55 kDa with greater than 97% purity. The stability analysis showed a half-life of over 4 years on storage at -80C

Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome

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Maki Fukami

2012-01-01

Full Text Available Aromatase excess syndrome (AEXS is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon. These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens.

Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives.

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Sahin, Zafer; Ertas, Merve; Berk, Barkın; Biltekin, Sevde Nur; Yurttas, Leyla; Demirayak, Seref

2018-05-01

Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition. In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC 50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC 50 :0.42 nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site. Copyright © 2018 Elsevier Ltd. All rights reserved.

Computational drug designing of fungal pigments as potential aromatase inhibitors

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Nighat Fatima

2014-12-01

Full Text Available The existing aromatase inhibitors produced unwelcome effects impose the discovery of novel drugs with privileged selectivity, a reduced amount of toxicity and humanizing potency. In this study, we illuminate the binding mode of polyketide azaphilanoid pigments monascin, ankaflavin, monascorubrin and monascorubramine isolated from Monascus fungus to the aromatase by molecular docking. The 3-dimensional structure of aromatase enzyme (PDB: 4KQ8 was obtained from the Protein Data Bank. PatchDock docking software was used to analyze structural complexes of the aromatase with monascus pigments. Comparatively, the AutoGrid model presented the most briskly constructive binding mode of monascin to aromatase. Docked energies in kcal/mol are: monascin;-13.2; monascorubramine:-12.8, monascorubrin:-12.3; ankaflavin: -10.5. These outcomes exposed these ligands could be potential drugs to treat hormone dependent breast cancer.

Aromatase and estrogen receptors in male reproduction.

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Carreau, Serge; Delalande, Christelle; Silandre, Dorothée; Bourguiba, Sonia; Lambard, Sophie

2006-02-26

Aromatase is a terminal enzyme which transforms irreversibly androgens into estrogens and it is present in the endoplasmic reticulum of numerous tissues. We have demonstrated that mature rat germ cells express a functional aromatase with a production of estrogens equivalent to that of Leydig cells. In humans in addition to Leydig cells, we have shown the presence of aromatase in ejaculated spermatozoa and in immature germ cells. In most tissues, high affinity estrogen receptors, ERalpha and/or ERbeta, mediate the role of estrogens. Indeed, in human spermatozoa, we have successfully amplified ERbeta mRNA but the protein was not detectable. Using ERalpha antibody we have detected two proteins in human immature germ cells: one at the expected size 66 kDa and another at 46 kDa likely corresponding to the ERalpha isoform lacking exon 1. In spermatozoa only the 46 kDa isoform was present, and we suggest that it may be located on the membrane. In addition, in men genetically deficient in aromatase, it is reported that alterations of spermatogenesis occur both in terms of the number and motility of spermatozoa. All together, these observations suggest that endogenous estrogens are important in male reproduction.

Aromatase Expression in the Hippocampus of AD Patients and 5xFAD Mice

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Janine Prange-Kiel

2016-01-01

Full Text Available Numerous studies show that 17β-estradiol (E2 protects against Alzheimer’s disease (AD induced neurodegeneration. The E2-synthesizing enzyme aromatase is expressed in healthy hippocampi, but although the hippocampus is severely affected in AD, little is known about the expression of hippocampal aromatase in AD. To better understand the role of hippocampal aromatase in AD, we studied its expression in postmortem material from patients with AD and in a mouse model for AD (5xFAD mice. In human hippocampi, aromatase-immunoreactivity was observed in the vast majority of principal neurons and signal quantification revealed higher expression of aromatase protein in AD patients compared to age- and sex-matched controls. The tissue-specific first exons of aromatase I.f, PII, I.3, and I.6 were detected in hippocampi of controls and AD patients by RT-PCR. In contrast, 3-month-old, female 5xFAD mice showed lower expression of aromatase mRNA and protein (measured by qRT-PCR and semiquantitative immunohistochemistry than WT controls; no such differences were observed in male mice. Our findings stress the importance of hippocampal aromatase expression in neurodegenerative diseases.

Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library.

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Chen, Shiuan; Hsieh, Jui-Hua; Huang, Ruili; Sakamuru, Srilatha; Hsin, Li-Yu; Xia, Menghang; Shockley, Keith R; Auerbach, Scott; Kanaya, Noriko; Lu, Hannah; Svoboda, Daniel; Witt, Kristine L; Merrick, B Alex; Teng, Christina T; Tice, Raymond R

2015-10-01

Multiple mechanisms exist for endocrine disruption; one nonreceptor-mediated mechanism is via effects on aromatase, an enzyme critical for maintaining the normal in vivo balance of androgens and estrogens. We adapted the AroER tri-screen 96-well assay to 1536-well format to identify potential aromatase inhibitors (AIs) in the U.S. Tox21 10K compound library. In this assay, screening with compound alone identifies estrogen receptor alpha (ERα) agonists, screening in the presence of testosterone (T) identifies AIs and/or ERα antagonists, and screening in the presence of 17β-estradiol (E2) identifies ERα antagonists. Screening the Tox-21 library in the presence of T resulted in finding 302 potential AIs. These compounds, along with 31 known AI actives and inactives, were rescreened using all 3 assay formats. Of the 333 compounds tested, 113 (34%; 63 actives, 50 marginal actives) were considered to be potential AIs independent of cytotoxicity and ER antagonism activity. Structure-activity analysis suggested the presence of both conventional (eg, 1, 2, 4, - triazole class) and novel AI structures. Due to their novel structures, 14 of the 63 potential AI actives, including both drugs and fungicides, were selected for confirmation in the biochemical tritiated water-release aromatase assay. Ten compounds were active in the assay; the remaining 4 were only active in high-throughput screen assay, but with low efficacy. To further characterize these 10 novel AIs, we investigated their binding characteristics. The AroER tri-screen, in high-throughput format, accurately and efficiently identified chemicals in a large and diverse chemical library that selectively interact with aromatase. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

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Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

2014-06-01

The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

International Nuclear Information System (INIS)

Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina; Lacorte, Sílvia; Porte, Cinta

2014-01-01

The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

Dry eye syndrome in aromatase inhibitor users.

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Turaka, Kiran; Nottage, Jennifer M; Hammersmith, Kristin M; Nagra, Parveen K; Rapuano, Christopher J

2013-04-01

Aromatase inhibitors are frequently used as an adjuvant therapy in the treatment of breast cancer. We observed that several patients taking aromatase inhibitors presented with severe dry eye symptoms, and we investigated whether there is a relationship between aromatase inhibitors and dry eyes in these patients. Retrospective chart review. Forty-one women. A computerized search of health records was performed to identify patients using anastrazole, letrozole and exemestane seen by the Cornea Service from August 2008 to March 2011. The results were compared with age-matched controls. Ocular surface changes among aromatase inhibitors users. Of the 41 women, 39 were Caucasians. Thirty-nine patients had breast cancer (95%), one patient had ovarian cancer (2.5%) and one had an unknown primary cancer. Mean age was 68 ± 11.3 years (range 47-95). Most common presenting symptoms were blurred vision in 28 (68%) patients, irritation/foreign body sensation in 12 (29%) patients, redness in 9 (22%) patients, tearing in 6 (22%) patients and photosensitivity in 2 (5%) patients. Mean Schirmer's test measurement was 11 ± 5.8 mm (range 0.5-20 mm). Blepharitis was noted in 68 of 82 eyes (73%), decreased or poor tear function in 24 eyes (29%), conjunctival injection in 18 eyes (22%) and superficial punctate keratitis in 12 eyes (29%). Among an age-matched population (45-95 years), dry eye syndrome was found in only 9.5% of patients. Because the prevalence of ocular surface disease signs and symptoms appears to be higher in study group than control patients, aromatase inhibitors might be a contributing factor to the dry eye symptoms. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

Genetics Home Reference: aromatase deficiency

Science.gov (United States)

... to impaired female sexual development, unusual bone growth, insulin resistance, and other signs and symptoms of aromatase deficiency . In women who are pregnant with an affected fetus, excess androgens in the ...

IGF-I stimulates ERβ and aromatase expression via IGF1R/PI3K/AKT-mediated transcriptional activation in endometriosis.

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Zhou, Yan; Zeng, Cheng; Li, Xin; Wu, Pei-Li; Yin, Ling; Yu, Xiao-Lan; Zhou, Ying-Fang; Xue, Qing

2016-08-01

Estrogen receptor beta (ERβ, encoded by ESR2 gene) and cytochrome P450 aromatase (encoded by CYP19A1 gene) play critical roles in endometriosis, and the levels of insulin-like growth factor-I (IGF-I) in the peritoneal fluid are significantly higher in patients with endometriosis compared with those in normal women. However, the effects and mechanisms of IGF-I on ERβ and aromatase expression remain to be fully elucidated. In this study, human endometriotic stromal cells (ESCs) and endometrial cells (EMs) derived from ovarian endometriomas and eutopic endometrial tissues. ESCs were cultured with IGF-I, signal pathway inhibitors, and siRNAs. ERβ and aromatase expression were measured by real-time PCR and Western, respectively. The binding of c-Jun and CREB to the ESR2 and CYP19A1 promoters was assessed by chromatin immunoprecipitation assay. Animal experiments were performed in a xenograft mouse model. Levels of IGF-I mRNA in ESCs were markedly higher than those in EMs. IGF-I upregulated ERβ and aromatase expression in ESCs after stimulation of the IGF1R/PI3K/AKT pathway. Following IGF-I treatment, a marked increase in c-Jun and CREB phosphorylation occurred, enhancing binding to the ESR2 and CYP19A1 promoters. An IGF1R inhibitor in vivo reduced IGF-I-induced endometriosis graft growth and ERβ and aromatase expression. In conclusion, this is the first report to describe a mechanistic analysis of ERβ and aromatase expression regulated by IGF-I in ESCs. Moreover, an IGF1R inhibitor impeded ectopic lesion growth in nude mice. These findings suggest that an inhibitor of IGF1R might have therapeutic potential as an antiendometriotic drug. Level of IGF-I mRNA in ESCs is markedly higher than that in EMs. IGF-I up-regulates ERβ and aromatase expression via IGF1R/PI3K/AKT pathway. C-Jun and CREB are recruited to ESR2 or CYP19A1 promoter by IGF-I stimulation. IGF-1R inhibitors in vivo impede the growth of ectopic lesions in nude mice.

Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

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Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2005-09-08

It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

Vaginal Gene Expression During Treatment With Aromatase Inhibitors.

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Kallak, Theodora Kunovac; Baumgart, Juliane; Nilsson, Kerstin; Åkerud, Helena; Poromaa, Inger Sundström; Stavreus-Evers, Anneli

2015-12-01

Aromatase inhibitor (AI) treatment suppresses estrogen biosynthesis and causes genitourinary symptoms of menopause such as vaginal symptoms, ultimately affecting the quality of life for many postmenopausal women with breast cancer. Thus, the aim of this study was to examine vaginal gene expression in women during treatment with AIs compared with estrogen-treated women. The secondary aim was to study the presence and localization of vaginal aromatase. Vaginal biopsies were collected from postmenopausal women treated with AIs and from age-matched control women treated with vaginal estrogen therapy. Differential gene expression was studied with the Affymetrix Gene Chip Gene 1.0 ST Array (Affymetrix Inc, Santa Clara, CA) system, Ingenuity pathway analysis, quantitative real-time polymerase chain reaction, and immunohistochemistry. The expression of 279 genes differed between the 2 groups; AI-treated women had low expression of genes involved in cell differentiation, proliferation, and cell adhesion. Some differentially expressed genes were found to interact indirectly with the estrogen receptor alpha. In addition, aromatase protein staining was evident in the basal and the intermediate vaginal epithelium layers, and also in stromal cells with a slightly stronger staining intensity found in AI-treated women. In this study, we demonstrated that genes involved in cell differentiation, proliferation, and cell adhesion are differentially expressed in AI-treated women. The expression of vaginal aromatase suggests that this could be the result of local and systemic inhibition of aromatase. Our results emphasize the role of estrogen for vaginal cell differentiation and proliferation and future drug candidates should be aimed at improving cell differentiation and proliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

Imaging of aromatase distribution in rat and rhesus monkey brains with [11C]vorozole

International Nuclear Information System (INIS)

Takahashi, Kayo; Bergstroem, Mats; Fraendberg, Pernilla; Vesstroem, Eva-Lotta; Watanabe, Yasuyoshi; Langstroem, Bengt

2006-01-01

Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [ 11 C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K d of [ 11 C]vorozole binding to aromatase in MA was determined to be 0.60±0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [ 11 C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons

Dopamine D1 receptor activation regulates the expression of the estrogen synthesis gene aromatase B in radial glial cell

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Lei eXing

2015-09-01

Full Text Available Radial glial cells (RGCs are abundant stem-like non-neuronal progenitors that are important for adult neurogenesis and brain repair, yet little is known about their regulation by neurotransmitters. Here we provide evidence for neuronal-glial interactions via a novel role for dopamine to stimulate RGC function. Goldfish were chosen as the model organism due to the abundance of RGCs and regenerative abilities of the adult central nervous system. A close anatomical relationship was observed between tyrosine hydroxylase-positive catecholaminergic cell bodies and axons and dopamine-D1 receptor expressing RGCs along the ventricular surface of telencephalon, a site of active neurogenesis. A primary cell culture model was established and immunofluorescence analysis indicates that in vitro RGCs from female goldfish retain their major characteristics in vivo, including expression of glial fibrillary acidic protein and brain lipid binding protein. The estrogen synthesis enzyme aromatase B is exclusively found in RGCs, but this is lost as cells differentiate to neurons and other glial types in adult teleost brain. Pharmacological experiments using the cultured RGCs established that specific activation of dopamine D1 receptors up-regulates aromatase B mRNA through a cyclic adenosine monophosphate-dependent molecular mechanism. These data indicate that dopamine enhances the steroidogenic function of this neuronal progenitor cell.

In Silico Prediction of Chemicals Binding to Aromatase with Machine Learning Methods.

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Du, Hanwen; Cai, Yingchun; Yang, Hongbin; Zhang, Hongxiao; Xue, Yuhan; Liu, Guixia; Tang, Yun; Li, Weihua

2017-05-15

Environmental chemicals may affect endocrine systems through multiple mechanisms, one of which is via effects on aromatase (also known as CYP19A1), an enzyme critical for maintaining the normal balance of estrogens and androgens in the body. Therefore, rapid and efficient identification of aromatase-related endocrine disrupting chemicals (EDCs) is important for toxicology and environment risk assessment. In this study, on the basis of the Tox21 10K compound library, in silico classification models for predicting aromatase binders/nonbinders were constructed by machine learning methods. To improve the prediction ability of the models, a combined classifier (CC) strategy that combines different independent machine learning methods was adopted. Performances of the models were measured by test and external validation sets containing 1336 and 216 chemicals, respectively. The best model was obtained with the MACCS (Molecular Access System) fingerprint and CC method, which exhibited an accuracy of 0.84 for the test set and 0.91 for the external validation set. Additionally, several representative substructures for characterizing aromatase binders, such as ketone, lactone, and nitrogen-containing derivatives, were identified using information gain and substructure frequency analysis. Our study provided a systematic assessment of chemicals binding to aromatase. The built models can be helpful to rapidly identify potential EDCs targeting aromatase.

Interactions between aromatase (estrogen synthase) and dopamine in the control of male sexual behavior in quail.

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Balthazart, Jacques; Baillien, Michelle; Ball, Gregory F

2002-05-01

In male quail, like in other vertebrates including rodents, testosterone acting especially through its estrogenic metabolites is necessary for the activation of male sexual behavior. Also, the administration of dopamine agonists and antagonists profoundly influences male sexual behavior. How the steroid-sensitive neural network and dopamine interact physiologically, remains largely unknown. It is often implicitly assumed that testosterone or its metabolite estradiol, stimulates male sexual behavior via the modification of dopaminergic transmission. We have now identified in quail two possible ways in which dopamine could potentially affect sexual behavior by modulating the aromatization of testosterone into an estrogen. One is a long-acting mechanism that presumably involves the modification of dopaminergic transmission followed by the alteration of the genomic expression of aromatase. The other is a more rapid mechanism that does not appear to be dopamine receptor-mediated and may involve a direct interaction of dopamine with aromatase (possibly via substrate competition). We review here the experimental data supporting the existence of these controls of aromatase activity by dopamine and discuss the possible contribution of these controls to the activation of male sexual behavior.

A pilot randomized trial to prevent sexual dysfunction in postmenopausal breast cancer survivors starting adjuvant aromatase inhibitor therapy.

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Advani, Pragati; Brewster, Abenaa M; Baum, George P; Schover, Leslie R

2017-08-01

A randomized pilot trial evaluated the hypothesis that early intervention lessens sexual dysfunction in the first year on aromatase inhibitors. A secondary aim was comparing the efficacy of two vaginal moisturizers. Fifty-seven postmenopausal women with early stage breast cancer starting aromatase inhibitors were randomized to three treatment groups. All received a handout on managing sexual and other side effects. The Usual Care group received no additional therapy. The Active Treatment groups received a 6-month supply of a vaginal moisturizer (hyaluronic acid-based in Active Group-H and prebiotic in Active Group-P) and a vaginal lubricant and dilator, plus access to an educational website and phone coaching. Questionnaires completed at baseline, 6, and 12 months included the Female Sexual Function Index (FSFI), Menopausal Sexual Interest Questionnaire (MSIQ), Female Sexual Distress Scale-Revised (FSDS-R), and a menopausal symptom scale. Forty-nine women (86%) provided follow-up data. Mean age was 59 and 77% were non-Hispanic Caucasian. Sexual function was impaired at baseline, but remained stable over 12 months for all groups. The combined active treatment group had less dyspareunia (P = 0.07) and sexual distress (P = 0.02) at 6 months than the Usual Care group. At 6 months, the Active-H group improved significantly more than the Active-P group on FSFI total score (P = 0.04). Sexual counseling helped women maintain stable sexual function on aromatase inhibitors. Active intervention resulted in better outcomes at 6 months. This promising pilot trial suggests a need for more research on preventive counseling to maintain sexual function during aromatase inhibitor treatment.

Ekspresi Gen CYP19 Aromatase, Estrogen, Androgen pada penderita Periodontitis Agresif

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Dahlia Herawati

2016-11-01

Full Text Available Kepadatan tulang tubuh ditentukan oleh gen CYP19 aromatase, hormon estrogen dan androgen. Pada periodontitis agresif terjadi perkembangan cepat kerusakan tulang alveolar, dan kerusakan tulang alveoler tersebut tidak diimbangioleh regenerasi tulang. Tujuan penelitian ini adalah menunjukkan ekspresi gen CYP19 aromatase, estrogen, androgen pada penderita periodontitis agresif agar dapat untuk menjadi pertimbangan pada saat melakukan perawatan periodontal. Metode penelitian, pemeriksaan ekspresi gen aromatse CYP19 berasal dari spesimen tulang alveolar menggunakan imunohistokimia, pengukuran hormon estrogen dan androgen dari serum menggunakan Vidas: Elfa. Hasil penelitian ekspresi gene CYP19 aromatase pada periodontitis agresif menunjukkan gambaran lebih rendah densitasnya dibandingkan pada nonperiodontitis. Estrogen dan androgen pad aperiodontitis agresif ada kecenderungan lebih rendah dibandingkan pada nonperiodontitis. Kesimpulan regenerasi tulang alveoler pad a periodontitis agresif terhambat karena sedikitnya gen CYP19 aromatase dan hormon estrogen dan androgen yang berperan pada pembentukan tulang alveoler kurang memadai.

Insight into the binding interactions of CYP450 aromatase inhibitors with their target enzyme: a combined molecular docking and molecular dynamics study.

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Galeazzi, Roberta; Massaccesi, Luca

2012-03-01

CYP450 aromatase catalyzes the terminal and rate-determining step in estrogen synthesis, the aromatization of androgens, and its inhibition is an efficient approach to treating estrogen-dependent breast cancer. Insight into the molecular basis of the interaction at the catalytic site between CYP450 aromatase inhibitors and the enzyme itself is required in order to design new and more active compounds. Hence, a combined molecular docking-molecular dynamics study was carried out to obtain the structure of the lowest energy association complexes of aromatase with some third-generation aromatase inhibitors (AIs) and with other novel synthesized letrozole-derived compounds which showed high in vitro activity. The results obtained clearly demonstrate the role of the pharmacophore groups present in the azaheterocyclic inhibitors (NSAIs)-namely the triazolic ring and highly functionalized aromatic moieties carrying H-bond donor or acceptor groups. In particular, it was pointed out that all of them can contribute to inhibition activity by interacting with residues of the catalytic cleft, but the amino acids involved are different for each compound, even if they belong to the same class. Furthermore, the azaheterocyclic group strongly coordinates with the Fe(II) of heme cysteinate in the most active NSAI complexes, while it prefers to adopt another orientation in less active ones.

Gonadal expression of Sf1 and aromatase during sex determination in the red-eared slider turtle (Trachemys scripta), a reptile with temperature-dependent sex determination.

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Ramsey, Mary; Shoemaker, Christina; Crews, David

2007-12-01

Many egg-laying reptiles have temperature-dependent sex determination (TSD), where the offspring sex is determined by incubation temperature during a temperature-sensitive period (TSP) in the middle third of development. The underlying mechanism transducing a temperature cue into an ovary or testis is unknown, but it is known that steroid hormones play an important role. During the TSP, exogenous application of estrogen can override a temperature cue and produce females, while blocking the activity of aromatase (Cyp19a1), the enzyme that converts testosterone to estradiol, produces males from a female-biased temperature. The production of estrogen is a key step in ovarian differentiation for many vertebrates, including TSD reptiles, and temperature-based differences in aromatase expression during the TSP may be a critical step in ovarian determination. Steroidogenic factor-1 (Sf1) is a key gene in vertebrate sex determination and regulates many steroidogenic enzymes, including aromatase. We find that Sf1 and aromatase are differentially expressed during sex determination in the red-eared slider turtle, Trachemys scripta elegans. Sf1 is expressed at higher levels during testis development while aromatase expression increases during ovary determination. We also assayed Sf1 and aromatase response to sex-reversing treatments via temperature or the modulation of estrogen availability. Sf1 expression was redirected to low-level female-specific patterns with feminizing temperature shift or exogenous estradiol application and redirected to more intense male-specific patterns with male-producing temperature shift or inhibition of aromatase activity. Conversely, aromatase expression was redirected to more intense female-specific patterns with female-producing treatment and redirected toward diffuse low-level male-specific patterns with masculinizing sex reversal. Our data do not lend support to a role for Sf1 in the regulation of aromatase expression during slider turtle sex

Testosterone-induced adult neurosphere growth is mediated by sexually-dimorphic aromatase expression

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Mark Ian Ransome

2015-07-01

Full Text Available We derived adult neural stem/progenitor cells (NSPCs from the sub-ventricular zone of male and female mice to examine direct responses to principal sex hormones. In the presence of epidermal growth factor (EGF and fibroblast growth factor-2 (FGF2 NSPCs of both sexes expressed nestin and sox2 and could be maintained as neurospheres without addition of any sex hormones. The reverse was not observed; neither testosterone (T, 17β-oestradiol (E2 nor progesterone (P4 was able to support neurosphere growth in the absence of EGF and FGF2. 10nM T, E2 or P4 induced nestin(+ cell proliferation within 20 minutes and enhanced neurosphere growth over 7 days irrespective of sex, which was abolished by Erk inhibition with 20M U0126. Maintaining neurospheres with each sex hormone did not affect subsequent neuronal differentiation. However, 10nM T, E2 or P4 added during differentiation increased III tubulin(+ neuron production with E2 being more potent compared to T and P4 in both sexes. Androgen receptor (AR inhibition with 20M flutamide but not aromatase inhibition with 10M letrozole reduced basal and T-induced neurosphere growth in females, while only concurrent inhibition of AR and aromatase produced the same effect in males. This sex-specific effect was supported by higher aromatase expression in male neurospheres compared to females measured by Western blot and green fluorescent protein reporter. 10M menadione induced oxidative stress, impaired neurosphere growth and up-regulated aromatase expression in both sexes. However, under oxidative stress letrozole significantly exacerbated impaired neurosphere growth in males only. While both E2 and T could prevent oxidative stress-induced growth reduction in both sexes, the effects of T were dependent on innate aromatase activity. We show for the first time that intrinsic androgen and estrogen signalling may impact the capacity of NSPCs to produce neural progenitors under pathological conditions of

Imaging of aromatase distribution in rat and rhesus monkey brains with [{sup 11}C]vorozole

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Takahashi, Kayo [Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala SE-75124 (Sweden); Uppsala Imanet, Uppsala SE-75109 (Sweden)]. E-mail: kayo.takahashi@uppsala.imanet.se; Bergstroem, Mats [Uppsala Imanet, Uppsala SE-75109 (Sweden); Department of Pharmaceutical Biosciences, Uppsala University, Uppsala SE-75124 (Sweden); Fraendberg, Pernilla [Uppsala Imanet, Uppsala SE-75109 (Sweden); Vesstroem, Eva-Lotta [Uppsala Imanet, Uppsala SE-75109 (Sweden); Watanabe, Yasuyoshi [Department of Physiology, Osaka City University Graduate School of Medicine, Osaka 545-8585 (Japan); Langstroem, Bengt [Uppsala Imanet, Uppsala SE-75109 (Sweden)

2006-07-15

Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [{sup 11}C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K {sub d} of [{sup 11}C]vorozole binding to aromatase in MA was determined to be 0.60{+-}0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [{sup 11}C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons.

Interaction of Zinc Chloride with an Aromatase Inhibitor (Letrozole on Anxiety in Adult Male Rats

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Sahar Charghan

2016-12-01

Full Text Available Abstract Background: Aromatase is an enzyme converts androstenedione and testosterone to estrone and estradiol, respectively. According to the role of testosterone and zinc in reducing anxiety and the relation between androgenic system function and zinc supplementations, in this research, the effect of zinc chloride injection was analysed in rats which aromatase enzyme was inhibited by aromatase inhibitor (letrozole. Materials and Methods: Adult male Wistar rats (weighing 225±25 g were used. Animals were divided into 12 groups and based on their weight, aromatase inhibitor (letrozole was injected (subcutaneously, and 30 minutes later, ZnCl2 or its solvent (saline was injected intra-peritoneal. Control group was received both solvents (DMSO and saline respectively. Anxiety levels were tested in the elevated plus maze 30 minutes after the last injection, and thereafter, open field was used for measurement of the locomotors activity of animals. Results: The results showed a significant decrease in the percentage of time spent in open arms in letrozole (1.25 mg/kg treated group as compared to that of solvent group. The locomotors activity significantly decreased between letrozole (1.25 mg/kg with the control group. The combined groups received letrozole (2.5 mg/kg and different amounts of zinc chloride (2.5, 5, 10 mg/kg, significantly reduced (p<0.05 the percentage of time spent in the open arm, comparing to the control group. Groups that received the combination of zinc chloride (2.5 mg/kg and different amounts of letrozole (1.25, 5, 10 mg/kg, showed no significant difference in the percentage of entry and time spent in the open arms. Conclusion: Totally, the present study suggests that letrozole alone increased anxiety and decreased locomotors activity and could interfere with anxiolytic effect of ZnCl2 as well.

Unique Distribution of Aromatase in the Human Brain: In Vivo Studies With PET and [N-Methyl-11C]Vorozole

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Biegon, A.; Biegon, A.; Kim, S.W.; Alexoff, D.; Millard, J.; Carter, P.; Hubbard, B.; King, P.; Logan, J.; Muench, L.; Pareto, D.; Schlyer, D.; Shea, C.; Telang, F.; Wang, G.-J.; Xu, Y.; Fowler, J.

2010-10-01

Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-{sup 11}C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V{sub T}) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region-dependent, ranging from {approx}70% blocking in thalamus andpreoptic area to {approx}10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.

Unique Distribution of Aromatase in the Human Brain: In Vivo Studies With PET and (N-Methyl-11C)Vorozole

International Nuclear Information System (INIS)

Biegon, A.; Kim, S.W.; Alexoff, D.; Millard, J.; Carter, P.; Hubbard, B.; King, P.; Logan, J.; Muench, L.; Pareto, D.; Schlyer, D.; Shea, C.; Telang, F.; Wang, G.-J.; Xu, Y.; Fowler, J.

2010-01-01

Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor (N-methyl- 11 C)vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V T ) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region-dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.

Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole.

Science.gov (United States)

Biegon, Anat; Kim, Sung Won; Alexoff, David L; Jayne, Millard; Carter, Pauline; Hubbard, Barbara; King, Payton; Logan, Jean; Muench, Lisa; Pareto, Deborah; Schlyer, David; Shea, Colleen; Telang, Frank; Wang, Gene-Jack; Xu, Youwen; Fowler, Joanna S

2010-11-01

Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-(11)C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V(T)) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced V(T) in all regions, though the size of the reduction was region-dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.

Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): is a clinical benefit still achievable?

Science.gov (United States)

Carlini, P; Frassoldati, A; De Marco, S; Casali, A; Ruggeri, E M; Nardi, M; Papaldo, P; Fabi, A; Paoloni, F; Cognetti, F

2001-11-01

There are few clinical data on the sequential use of aromatase inhibitors (AI). This paper focuses on the relevance of clinical benefit CB (CR + PR + SD > or = 6 months) in postmenopausal metastatic breast cancer (MBC) patients treated with the steroidal aromatase inhibitor (SAI) formestane (FOR). who had already received non-steroidal aromatase inhibitor (nSAI): letrozole (LTZ) or anastrozole (ANZ). Twenty postmenopausal women with MBC were analysed in this retrospective two-centre study with the sequence nSAI-FOR. When receiving ANZ, 1 of 11 achieved a complete response and 9 of 11 a stable disease > or = 6 months, and receiving LTZ 1 of 9 achieved a partial response and 4 of 9 a stable disease > or = 6 months. The analysis of the entire population treated with FOR showed an overall CB of 55% (11 of 20) with a median duration of 15 months and median time to progression (TTP) of 6 months. Formestane 250 mg once bi-weekly seems to be an attractive alternative third-line hormonal therapy for the treatment of patients with MBC, previously treated with nSAI.

Mechanism-based Categorization of Aromatase Inhibitors: A Potential Discovery and Screening Tool

Science.gov (United States)

Cytochrome P450 aromatase is a key steroidogenic enzyme that converts androgens to estrogens in vertebrates. There is much interest in aromatase inhibitors (AIs) because a number of environmental contaminants can act as AIs, thereby disrupting endocrine function in humans and wil...

Reinvestigation of the synthesis and evaluation of [N-methyl-11C]vorozole, a radiotracer targeting cytochrome P450 aromatase

International Nuclear Information System (INIS)

Kim, Sung Won; Biegon, Anat; Katsamanis, Zachary E.; Ehrlich, Carolin W.; Hooker, Jacob M.; Shea, Colleen; Muench, Lisa; Xu Youwen; King, Payton; Carter, Pauline; Alexoff, David L.; Fowler, Joanna S.

2009-01-01

Introduction: We reinvestigated the synthesis of [N-methyl- 11 C]vorozole, a radiotracer for aromatase, and discovered the presence of an N-methyl isomer which was not removed in the original purification method. Herein we report the preparation and positron emission tomography (PET) studies of pure [N-methyl- 11 C]vorozole. Methods: Norvorozole was alkylated with [ 11 C]methyl iodide as previously described and also with unlabeled methyl iodide. A high-performance liquid chromatography (HPLC) method was developed to separate the regioisomers. Nuclear magnetic resonance (NMR) spectroscopy ( 13 C and 2D-nuclear Overhauser effect spectroscopy NMR) was used to identify and assign structures to the N-methylated products. Pure [N-methyl- 11 C]vorozole and the contaminating isomer were compared by PET imaging in the baboon. Results: Methylation of norvorozole resulted in a mixture of isomers (1:1:1 ratio) based on new HPLC analysis using a pentafluorophenylpropyl bonded silica column, in which vorozole coeluted one of its isomers under the original HPLC conditions. Baseline separation of the three labeled isomers was achieved. The N-3 isomer was the contaminant of vorozole, thus correcting the original assignment of isomers. PET studies of pure [N-methyl- 11 C]vorozole with and without the contaminating N-3 isomer revealed that only [N-methyl- 11 C]vorozole binds to aromatase. [N-methyl- 11 C]Vorozole accumulated in all brain regions with highest accumulation in the aromatase-rich amygdala and preoptic area. Accumulation was blocked with vorozole and letrozole consistent with reports of some level of aromatase in many brain regions. Conclusions: The discovery of a contaminating labeled isomer and the development of a method for isolating pure [N-methyl- 11 C]vorozole combine to provide a new scientific tool for PET studies of the biology of aromatase and for drug research and development.

Localization of the aromatase enzyme expression in the human pituitary gland and its effect on growth hormone, prolactin, and thyroid stimulating hormone axis.

Science.gov (United States)

Caglar, Asli Sezgin; Kapucu, Aysegul; Dar, Kadriye Akgun; Ozkaya, Hande Mefkure; Caglar, Erkan; Ince, Haluk; Kadioglu, Pinar

2015-08-01

The aim of this study is to evaluate aromatase expression in prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) secreting cells. Nontumoral human pituitary specimens were obtained from autopsy samples. Aromatase co-expression was determined by double immunohistochemical staining and assessed using H scores. H scores for GH-aromatase co-expression (GH-aromatase), TSH-aromatase co-expression (TSH-aromatase), and PRL-aromatase co-expression (PRL-aromatase) were 83.1 ± 13.1, 95.6 ± 16.1, and 83.7 ± 14.5, respectively. TSH producing cells exhibited the highest H score for co-expression of aromatase (p 0.05 for all). There was a negative correlation between the H scores for aromatase and PRL-aromatase, GH-aromatase and TSH-aromatase, respectively (r = -0.592, p 0.05 for all). Age was negatively correlated with PRL-aromatase H score (r = -0.373, p = 0.008). Our study demonstrated significant aromatase co-expression in PRL, GH, and TSH secreting cells of the human anterior pituitary gland. The mutual paracrinal regulation between aromatase and three adenohypophyseal hormones indicates that aromatase may have a regulatory role on the synthesis and secretion of these hormones.

Big enough for an aromatase inhibitor? How adiposity affects male fertility.

Science.gov (United States)

Stephens, Sahar M; Polotsky, Alex J

2013-07-01

Obesity is a pandemic and is associated with multiple medical problems including subfertility. Male obesity has been associated with altered semen parameters and reproductive hormonal levels, including a reduced testosterone:estradiol (T:E₂) ratio. Treatment methods employed for obesity-related male subfertility include gonadotropin administration, weight loss, and aromatase inhibitors. Letrozole is a highly effective nonsteroidal aromatase inhibitor that has been used to treat male subfertility in several case series with promising results. Adequately designed randomized controlled studies are needed to produce evidence-based data on the role of aromatase inhibitors in male subfertility management and evaluate the side-effect profile. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women

International Nuclear Information System (INIS)

Biegon, Anat; Fowler, Joanna S.; Alexoff, David L.; Kim, Sung Won; Logan, Jean; Pareto, Deborah; Schlyer, David; Wang, Gene-Jack

2015-01-01

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with (11)C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aims to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathological situations can be studied. Methods: (11)C-vorozole (111-296 MBq/subject) was injected I.V in 13 men and 20 women (age range 23 to 67). PET data were acquired over a 90 minute period. Each subject had 4 scans, 2/day separated by 2-6 weeks, including brain and torso or pelvis scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned following pretreatment with a clinical dose of the aromatase inhibitor letrozole.Time activity curves were obtained and standard uptake values (SUV) calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole body radiation exposures were calculated using Olinda software. Results: Liver uptake was higher than all other organs, but was not blocked by pretreatment with letrozole. Mean SUVs in men were higher than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than all other organs (ranging from 0.48±0.05 in lungs to 1.5±0.13 in kidneys). Mean ovarian SUVs (3.08±0.7) were comparable to brain levels and higher than all other organs. Furthermore, ovarian SUVs In young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, while aging and cigarette smoking reduced (11)C-vorozole uptake. Conclusions: PET with (11)C-vorozole is useful for assessing physiological changes in estrogen synthesis capacity in the human body. Baseline levels in

Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects.

Science.gov (United States)

Berstein, Lev; Maximov, Sergei; Gershfeld, Eduard; Meshkova, Irina; Gamajunova, Vera; Tsyrlina, Evgenia; Larionov, Alexei; Kovalevskij, Anatolii; Vasilyev, Dmitry

2002-11-15

To investigate the short-term hormonal and clinical effects of the aromatase inhibitor letrozole (Femara) in patients with endometrial cancer. Ten previously untreated, post-menopausal patients (mean age 59 years) with endometrial cancer, predominantly stage I disease, received letrozole 2.5mg per day for 14 days before surgery. Clinical, sonographic, morphologic, cytologic, and hormonal-metabolic parameters (blood estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and cholesterol by radioimmunoassay, enzyme immune assay, or enzyme-colorimetric methods; tumor progesterone receptors by ligand-binding assay; and aromatase activity by 3H-water release assay) were evaluated before and after treatment. Treatment was well-tolerated in all patients. In two patients, pain relief in the lower part of the belly and/or decrease in intensity of uterine discharge was reported. In the three cases, substantial decreases in endometrial M-echo (ultrasound) signal were noted; the mean value of this parameter after treatment was 31.1% lower than before treatment. Blood estradiol concentration decreased by an average of 37.8% after letrozole therapy, and tumor progesterone receptor levels and aromatase activity decreased by 34.4 and 17.5%, respectively. Treatment with letrozole did not influence surgery. These data show that short-term treatment with letrozole in the neoadjuvant setting resulted in some positive clinical changes. Longer-term and larger-scale trials of neoadjuvant letrozole in endometrial cancer are warranted.

Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence with Oestrogen Receptors α and β, and Androgen Receptors

Science.gov (United States)

Stanić, Davor; Dubois, Sydney; Chua, Hui Kheng; Tonge, Bruce; Rinehart, Nicole; Horne, Malcolm K.; Boon, Wah Chin

2014-01-01

Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα−, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females. PMID:24646567

Post-proliferative immature radial glial cells female-specifically express aromatase in the medaka optic tectum.

Directory of Open Access Journals (Sweden)

Akio Takeuchi

Full Text Available Aromatase, the key enzyme responsible for estrogen biosynthesis, is present in the brain of all vertebrates. Much evidence has accumulated that aromatase is highly and exclusively expressed in proliferating mature radial glial cells in the brain of teleost fish even in adulthood, unlike in other vertebrates. However, the physiological significance of this expression remains unknown. We recently found that aromatase is female-specifically expressed in the optic tectum of adult medaka fish. In the present study, we demonstrated that, contrary to the accepted view of the teleost brain, female-specific aromatase-expressing cells in the medaka optic tectum represent a transient subset of post-proliferative immature radial glial cells in the neural stem cell lineage. This finding led us to hypothesize that female-specific aromatase expression and consequent estrogen production causes some sex difference in the life cycle of tectal cells. As expected, the female tectum exhibited higher expression of genes indicative of cell proliferation and radial glial maturation and lower expression of an anti-apoptotic gene than did the male tectum, suggesting a female-biased acceleration of the cell life cycle. Complicating the interpretation of this result, however, is the additional observation that estrogen administration masculinized the expression of these genes in the optic tectum, while simultaneously stimulating aromatase expression. Taken together, these results provide evidence that a unique subpopulation of neural stem cells female-specifically express aromatase in the optic tectum and suggest that this aromatase expression and resultant estrogen synthesis have an impact on the life cycle of tectal cells, whether stimulatory or inhibitory.

Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

International Nuclear Information System (INIS)

Biegon, A.; Kim, S.-W.; Logan, J.; Hooker, J.M.; Muench, L.; Fowler, J.S.

2010-01-01

Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor ( 11 C)vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Nicotine administration produced significant, dose-dependent reductions in ( 11 C)vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.

Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19)

Energy Technology Data Exchange (ETDEWEB)

Guo, Jiajia [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Yuan, Yun [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang (China); Lu, Danfeng; Du, Baowen [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Xiong, Liang; Shi, Jiangong [State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Yang, Lijuan [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Liu, Wanli [MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084 (China); Yuan, Xiaohong [School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang (China); Zhang, Guolin, E-mail: zhanggl@cib.ac.cn [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu (China); Wang, Fei, E-mail: wangfei@cib.ac.cn [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu (China)

2014-08-15

Aromatase is the only enzyme in vertebrates to catalyze the biosynthesis of estrogens. Although inhibitors of aromatase have been developed for the treatment of estrogen-dependent breast cancer, the whole-body inhibition of aromatase causes severe adverse effects. Thus, tissue-selective aromatase inhibitors are important for the treatment of estrogen-dependent cancers. In this study, 63 natural products with diverse structures were examined for their effects on estrogen biosynthesis in human ovarian granulosa-like KGN cells. Two compounds—trans-phytol (SA-20) and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol (SA-48)—were found to potently inhibit estrogen biosynthesis (IC{sub 50}: 1 μM and 0.5 μM, respectively). Both compounds decreased aromatase mRNA and protein expression levels in KGN cells, but had no effect on the aromatase catalytic activity in aromatase-overexpressing HEK293A cells and recombinant expressed aromatase. The two compounds decreased the expression of aromatase promoter I.3/II. Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). The effects of these two compounds on extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were examined. Inhibition of p38 MAPK could be the mechanism underpinning the actions of these compounds. Our results suggests that natural products structurally similar to SA-20 and SA-48 may be a new source of tissue-selective aromatase modulators, and that p38 MAPK is important in the basal control of aromatase in ovarian granulosa cells. SA-20 and SA-48 warrant further investigation as new pharmaceutical tools for the prevention and treatment of estrogen-dependent cancers. - Highlights: • Two natural products inhibited estrogen biosynthesis in human ovarian granulosa cells. • They

Reinvestigation of the synthesis and evaluation of [N-methyl-{sup 11}C]vorozole, a radiotracer targeting cytochrome P450 aromatase

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Won [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)], E-mail: swkim@bnl.gov; Biegon, Anat; Katsamanis, Zachary E. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Ehrlich, Carolin W. [Johannes-Gutenberg Universitaet Mainz, Institut fuer Organische Chemie, Duesbergweg 10-14, Mainz (Germany); Hooker, Jacob M.; Shea, Colleen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Muench, Lisa [National Institute on Alcoholism and Alcohol Abuse, Bethesda, MD (United States); Xu Youwen; King, Payton; Carter, Pauline; Alexoff, David L. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Psychiatry, Mount Sinai School of Medicine, New York, NY (United States); Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY (United States)

2009-04-15

Introduction: We reinvestigated the synthesis of [N-methyl-{sup 11}C]vorozole, a radiotracer for aromatase, and discovered the presence of an N-methyl isomer which was not removed in the original purification method. Herein we report the preparation and positron emission tomography (PET) studies of pure [N-methyl-{sup 11}C]vorozole. Methods: Norvorozole was alkylated with [{sup 11}C]methyl iodide as previously described and also with unlabeled methyl iodide. A high-performance liquid chromatography (HPLC) method was developed to separate the regioisomers. Nuclear magnetic resonance (NMR) spectroscopy ({sup 13}C and 2D-nuclear Overhauser effect spectroscopy NMR) was used to identify and assign structures to the N-methylated products. Pure [N-methyl-{sup 11}C]vorozole and the contaminating isomer were compared by PET imaging in the baboon. Results: Methylation of norvorozole resulted in a mixture of isomers (1:1:1 ratio) based on new HPLC analysis using a pentafluorophenylpropyl bonded silica column, in which vorozole coeluted one of its isomers under the original HPLC conditions. Baseline separation of the three labeled isomers was achieved. The N-3 isomer was the contaminant of vorozole, thus correcting the original assignment of isomers. PET studies of pure [N-methyl-{sup 11}C]vorozole with and without the contaminating N-3 isomer revealed that only [N-methyl-{sup 11}C]vorozole binds to aromatase. [N-methyl-{sup 11}C]Vorozole accumulated in all brain regions with highest accumulation in the aromatase-rich amygdala and preoptic area. Accumulation was blocked with vorozole and letrozole consistent with reports of some level of aromatase in many brain regions. Conclusions: The discovery of a contaminating labeled isomer and the development of a method for isolating pure [N-methyl-{sup 11}C]vorozole combine to provide a new scientific tool for PET studies of the biology of aromatase and for drug research and development.

Overexpression of aromatase alone is sufficient for ovarian development in genetically male chicken embryos.

Directory of Open Access Journals (Sweden)

Luke S Lambeth

Full Text Available Estrogens play a key role in sexual differentiation of both the gonads and external traits in birds. The production of estrogen occurs via a well-characterised steroidogenic pathway, which is a multi-step process involving several enzymes, including cytochrome P450 aromatase. In chicken embryos, the aromatase gene (CYP19A1 is expressed female-specifically from the time of gonadal sex differentiation. To further explore the role of aromatase in sex determination, we ectopically delivered this enzyme using the retroviral vector RCASBP in ovo. Aromatase overexpression in male chicken embryos induced gonadal sex-reversal characterised by an enlargement of the left gonad and development of ovarian structures such as a thickened outer cortex and medulla with lacunae. In addition, the expression of key male gonad developmental genes (DMRT1, SOX9 and Anti-Müllerian hormone (AMH was suppressed, and the distribution of germ cells in sex-reversed males followed the female pattern. The detection of SCP3 protein in late stage sex-reversed male embryonic gonads indicated that these genetically male germ cells had entered meiosis, a process that normally only occurs in female embryonic germ cells. This work shows for the first time that the addition of aromatase into a developing male embryo is sufficient to direct ovarian development, suggesting that male gonads have the complete capacity to develop as ovaries if provided with aromatase.

Teratogenicity and brain aromatase-induction of monosodium ...

African Journals Online (AJOL)

Teratogenicity and brain aromatase-induction of monosodium glutamate in estrogen-responsive mosaic transgenic zebra fish Danio rerio. Tamer Said Abdelkader, Chang Seo-Na, Kim Tae-Hyun, Song Juha, Kim Dongso, Jae-Hak Park ...

Inhibition of human aromatase complex (CYP19) by antiepileptic drugs

DEFF Research Database (Denmark)

Jacobsen, Naja Wessel; Halling-Sørensen, Bent; Birkved, Franziska Maria A Kramer

2008-01-01

of 1.4-49.7 mM. Carbamazepine, gabapentin, primidone, topiramate and vigabatrin showed no inhibition. Additionally, binary drug combinations were tested to investigate if combination therapy could potentiate the aromatase inhibition. Additive inhibition was seen in combination experiments...... with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered....

Aromatase imaging with [N-methyl-11C]vorozole PET in healthy men and women.

Science.gov (United States)

Biegon, Anat; Alexoff, David L; Kim, Sung Won; Logan, Jean; Pareto, Deborah; Schlyer, David; Wang, Gene-Jack; Fowler, Joanna S

2015-04-01

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with (11)C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aimed to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathologic situations can be studied. (11)C-vorozole (111-296 MBq/subject) was injected intravenously in 13 men and 20 women (age range, 23-67 y). PET data were acquired over a 90-min period. Each subject had 4 scans, 2 per day separated by 2-6 wk, including brain and torso or pelvis scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned after pretreatment with a clinical dose of the aromatase inhibitor letrozole. Time-activity curves were obtained, and standardized uptake values (SUV) were calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone, and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole-body radiation exposures were calculated using OLINDA software. Liver uptake was higher than uptake in any other organ but was not blocked by pretreatment with letrozole. Mean SUVs were higher in men than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than SUVs in any other organ (ranging from 0.48 ± 0.05 in lungs to 1.5 ± 0.13 in kidneys). Mean ovarian SUVs (3.08 ± 0.7) were comparable to brain levels and higher than in any other organ. Furthermore, ovarian SUVs in young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, whereas aging and cigarette smoking reduced (11)C-vorozole uptake. PET with (11)C-vorozole is useful for assessing physiologic changes in estrogen synthesis capacity in the human body. Baseline levels

DIFERENSIASI KELAMIN TIGA GENOTIPE IKAN NILA YANG DIBERI BAHAN AROMATASE INHIBITOR

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Didik Ariyanto

2016-11-01

Full Text Available Penggunaan hormon sintetik 17 a-metiltestosterone untuk sex reversal ikan konsumsi sudah dilarang. Salah satu bahan yang terbukti efektif dalam sex reversal adalah bahan aromatase inhibitor. Bahan ini dapat digunakan dalam proses pembalikan kelamin karena menghambat sekresi enzim aromatase yang bertanggung jawab dalam konversi hormon androgen menjadi estrogen. Tingginya kadar androgen dalam tubuh akan mengarahkan proses diferensiasi kelamin ke arah kelamin jantan. Penelitian ini bertujuan mengetahui pengaruh pemberian bahan aromatase inhibitor terhadap diferensiasi kelamin tiga genotipe ikan nila. Bahan utama yang digunakan adalah larva ikan nila genotipe XX, XY, dan YY yang diberi bahan aromatase inhibitor, khususnya imidazole. Penambahan hormon sintetik 17a-metiltestosterone digunakan sebagai kontrol (+. Pemberian imidazole dilakukan melalui pakan pada larva ikan nila yang berumur 7 hari setelah menetas, selama 28 hari. Selanjutnya benih dipelihara dalam hapa pendederan selama 60 hari di kolam tanah. Pada akhir pendederan dilakukan identifikasi jenis kelamin, bobot individu rata-rata, dan sintasan. Hasil penelitian menunjukkan bahwa imidazole efektif meningkatkan rasio kelamin jantan pada ikan nila genotipe XX dan YY, tetapi tidak pada genotipe XY. Sampai akhir tahap pendederan, semua genotipe dan perlakuan yang berbeda tidak memberikan efek yang berbeda nyata terhadap laju pertumbuhan maupun nilai sintasan, kecuali pada genotipe YY

Merlin, the product of NF2 gene, is associated with aromatase expression and estrogen formation in human liver tissues and liver cancer cells.

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Cocciadiferro, Letizia; Miceli, Vitale; Granata, Orazia M; Carruba, Giuseppe

2017-09-01

The product of neurofibromatosis type 2 (NF2) gene, also known as Merlin/neurofibromin 2, homeostatically regulates liver stem cells by controlling abundance and signaling of epidermal growth factor receptor (EGFR), with a mechanism independent of the Hippo pathway. We have reported that locally elevated estrogen formation, driven by abnormally high expression and function of aromatase, may be implicated in development and progression of human hepatocellular carcinoma (HCC) through activation of a rapid signaling pathway mediated by amphiregulin (AREG) and EGFR. We have recently presented a model by which the aromatase-estrogen-amphiregulin-EGFR axis is activated in response to tissue injury and/or inflammatory disease, with its alteration eventually leading to development of major human tumors (liver, breast, prostate) and other chronic diseases (diabetes, obesity, Alzheimer's and heart disease). In this study, we investigated NF2 expression in liver cancer cells and tissues in relation to aromatase expression/function, estrogen receptor (ER) status and amphiregulin. Our data indicate that NF2 expression is associated with aromatase and AREG expression, being elevated in HCC tissues and HepG2 cells, intermediate in cirrhotic tissues and Huh7 cells, and lower in nontumoral liver and HA22T cells. In addition, NF2 expression is inversely related to wild type hERα66 and proportional to the expression of the membrane-associated hERα36 splice variant, as measured by exon-specific RT-PCR analysis, both in vivo and in vitro. Furthermore, incubation with estradiol induced a significant decrease of NF2 expression in both HA22T and Huh7 cells (over 54% and 22%, respectively), while no change could be observed in HepG2 cells, this effect being inversely related to aromatase expression and activity in HCC cell lines. Based on the above combined evidence, we hypothesize that NF2 behaves as a protein sensing tissue damage and aromatase-driven local estrogen formation

Correlation between aromatase expression in the eutopic endometrium of symptomatic patients and the presence of endometriosis

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Maia Jr H

2012-02-01

Full Text Available Hugo Maia Jr1,2, Clarice Haddad1,2, Julio Casoy11CEPARH, 2Itaigara Memorial Day Hospital, Salvador, Bahia, BrazilObjective: To investigate whether aromatase expression in the eutopic endometrium correlates with the presence and severity of endometriosis in patients with infertility and/or dysmenorrhea undergoing laparoscopy and hysteroscopy.Patients: The study involved 106 patients of reproductive age with symptoms of dysmenorrhea and infertility. Sixteen endometriosis-free asymptomatic patients were used as a control group.Methods: Concomitant laparoscopy and hysteroscopy was carried out in all cases. An endometrial biopsy was taken to determine aromatase p450 expression by immunohistochemistry. Endometriosis was staged according to the American Society of Reproductive Medicine classification.Results: Endometriosis was diagnosed by laparoscopy in 92/106 symptomatic patients. In this group, aromatase expression was detected in the eutopic endometrium of 66/92 patients with endometriosis (72% and in 13/14 (95% patients in the symptomatic, endometriosis-free group (P = 0.09. Aromatase expression was not detected in any patients from the control group. In the endometriosis group, aromatase expression was detected in the eutopic endometrium of 28/45 patients (62% with American Society of Reproductive Medicine classification stage 1 of the disease, in 11/14 patients (78% with stage II, 14/20 patients (70% with stage III, and in 12/13 patients (92% with stage IV; however, the difference was only statistically significant between stages I and IV (P = 0.04.Conclusion: Aromatase expression in the endometrium was associated with the presence of dysmenorrhea and infertility irrespective of the presence of endometriosis. When endometriosis was present, however, there was a tendency for aromatase expression to be positively correlated with dysmenorrhea severity.Keywords: aromatase, endometrium, endometriosis, Cox-2, dysmenorrhea

Synthesis and PET studies of [(11)C-cyano]letrozole (Femara), an aromatase inhibitor drug.

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Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J; Fowler, Joanna S

2009-02-01

Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K(i)=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [(11)C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [(11)C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [(11)C-cyano]letrozole fraction in arterial plasma were also measured. [(11)C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16+/-2.21 Ci/mumol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. [(11)C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [(11)C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as amygdala, which are known to

Sex change strategy and the aromatase genes.

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Gardner, L; Anderson, T; Place, A R; Dixon, B; Elizur, A

2005-04-01

Sequential hermaphroditism is a common reproductive strategy in many teleosts. Steroid production is known to mediate both the natural and induced sex change, yet beyond this the physiology directing this process has received little attention. Cytochrome P450 aromatase is a key enzyme in the hormonal pathway catalysing the conversion of sex steroids, androgens to oestrogens, and thus is highly relevant to the process of sex change. This study reports the isolation of cDNA sequences for aromatase isoforms CYP19A1 and CYP19A2 from teleost species representing three forms of sexual hermaphroditism: Lates calcarifer (protandry), Cromileptes altivelis (protogyny), and Gobiodon histrio (bi-directional). Deduced amino acid analysis of these isoforms with other reported isoforms from gonochoristic (single sex) teleosts revealed 56-95% identity within the same isoform while only 48-65% identity between isoforms irrespective of species and sexual strategy. Phylogenetic analysis supported this result separating sequences into isoform exclusive clades in spite of species apparent evolutionary distance. Furthermore, this study isolates 5' flanking regions of all above genes and describes putative cis-acting elements therein. Elements identified include steroidogenic factor 1 binding site (SF-1), oestrogen response element (ERE), progesterone response element (PRE), androgen response element (ARE), glucocorticoid response elements (GRE), peroxisome proliferator-activated receptor alpha/retinoid X receptor alpha heterodimer responsive element (PPARalpha/RXRalpha), nuclear factor kappabeta (NF-kappabeta), SOX 5, SOX 9, and Wilms tumor suppressor (WTI). A hypothetical in vivo model was constructed for both isoforms highlighting potential roles of these putative cis-acting elements with reference to normal function and sexual hermaphroditism.

Pemodelan Molekul Turunan p-Metoksi sinnamoil Hidrazida Sebagai Inhibitor Checkpoint Kinase 1 dan Inhibitor Aromatase secara In silico

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Galih Satrio Putra

2017-08-01

Full Text Available The development of anticancer drugs from ethyl p-methoxycinnamate (EPMC derivatives continues to obtain compounds that have high ability of cancer cells apoptosis and minimal side effects. p-Methoxycinnamoyl hydrazide derivate compounds from EPMC structure modification were docked into the ligand-binding pocket of Check point kinase 1 enzymes (2YWP and the aromatase enzyme (3S7S using software Molegro Virtual Docker (MVD Ver.5.5. We compared the Rerank score of native ligand with derivate compounds of p-Methoxycinnamoyl hydrazide. Rerank scores of compounds 4b and 4c (-99.98 Kcal/mol and -99.80 Kcal/mol were lower than the native ligand A42 in inhibiting the enzyme checkpoint kinase 1. Rerank values of p-Methoxycinnamoyl hydrazide derivate compounds were greater than the native ligand EXM in inhibiting the enzyme aromatase. p-Methoxycinnamoyl hydrazide derivate compounds, especially compounds 4b and 4c, had anticancer mechanism by inhibiting the enzyme pathway checkpoint kinase 1 and had not activity in inhibiting the aromatase enzyme.

Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like symptomatology.

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Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2004-07-01

We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or 'depressive-like' symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild-type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit 'depressive-like' symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the 'depressive-like' profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression.

Efficacy and mechanism of action of Proellex, an antiprogestin in aromatase overexpressing and Letrozole resistant T47D breast cancer cells.

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Gupta, Akash; Mehta, Rajeshwari; Alimirah, Fatouma; Peng, Xinjian; Murillo, Genoveva; Wiehle, Ronald; Mehta, Rajendra G

2013-01-01

Aromatase inhibitors (AI) are considered as a first line therapy for ER+PR+ breast cancers. However, many patients acquire resistance to AI. In this study, we determined the response of antiprogestin CDB-4124 (Proellex) on the aromatase overexpressing and Letrozole resistant cell lines and also studies its mechanism of action in inhibition of breast cancer cell proliferation. For these studies we generated aromatase overexpressing T47D (T47Darom) and respective control (T47Dcon) breast cancer cell lines by stable transfection with plasmid containing CYP19A1 gene, or empty vector respectively. Letrozole resistant cell line (T47DaromLR) was generated by incubating T47Darom for 75 weeks in the presence of 10 μM Letrozole. Cell proliferation was determined by MTT or crystal violet assays. Gene expressions were quantified by QRT-PCR whereas proteins were identified by western blot analyses, flow cytometry and immunofluorescence staining. Aromatase activity was determined by estradiol ELISA. The effects of Proellex on the anchorage independent growth were measured by soft agar colony formation. Statistical differences between the various groups were determined by Student's 't' test or ANOVA followed by Bonferroni's post hoc test. Results showed that T47Darom and T47DaromLR cell lines had significantly higher aromatase expression (mRNA; 80-90 fold and protein) and as a result exhibited increased aromatization of testosterone to estradiol as compared to T47Dcon. Both these cell lines showed enhanced growth in the presence of Testosterone (50-60%). In T47DaromLR cells increased PR-B and EGFR expression as compared to T47Dcon cells was observed. Proellex and other known aromatase inhibitors (Letrozole, Anastrozole, and Exemestane) inhibited testosterone induced cell proliferation and anchorage independent growth of T47Darom cells. Cell growth inhibition was significantly greater when cells were treated with Proellex alone or in combination with other AIs as compared to AIs

Synthesis and PET studies of [{sup 11}C-cyano]letrozole (Femara), an aromatase inhibitor drug

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Kil, Kun-Eek [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, Stony Brook University, Stony Brook, NY 11794 (United States); Biegon, Anat [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Ding, Yu-Shin [Department of Radiology, Yale University School of Medicine, New Haven, CT 06520-8048 (United States); Fischer, Andre [Johannes-Gutenberg Universitaet Mainz, Institut fuer Organische Chemie, 55128 Mainz (Germany); Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, Stony Brook University, Stony Brook, NY 11794 (United States)], E-mail: fowler@bnl.gov

2009-02-15

Introduction: Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K{sub i}=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods: Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [{sup 11}C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [{sup 11}C-cyano]letrozole fraction in arterial plasma were also measured. Results: [{sup 11}C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16{+-}2.21 Ci/{mu}mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. Conclusion: [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [{sup 11}C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity

Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug

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Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J.; Fowler, Joanna S.

2011-01-01

Introduction Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara®) is a high affinity aromatase inhibitor (Ki=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [11C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [11C-cyano]letrozole fraction in the arterial plasma were also measured. Results [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79–80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. Conclusion [11C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain

Leptin stimulates aromatase in the growth plate: limiting catch-up growth efficiency.

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Masarwi, Majdi; Shamir, Raanan; Phillip, Moshe; Gat-Yablonski, Galia

2018-06-01

Catch-up growth (CUG) in childhood is defined as periods of growth acceleration, after the resolution of growth attenuation causes, bringing the children back to their original growth trajectory. Sometimes, however, CUG is incomplete, leading to permanent growth deficit and short stature. The aim of this study was to investigate the mechanisms that limit nutritional-CUG. Specifically, we focused on the crosstalk between leptin, increased by re-feeding, and sex hormones, which increase with age. In vivo studies were performed in young male Sprague Dawley rats fed ad libitum or subjected to 10/36 days of 40% food restriction followed by 90-120 days of re-feeding. In vitro studies were performed on ATDC5 cells. Analyses of mRNA and protein levels were done using qPCR and Western blot, respectively. CUG was complete in body weight and humerus length in animals that were food-restricted for 10 days but not for those food-restricted for 36 days. In vitro studies showed that leptin significantly increased aromatase gene expression and protein level as well as the expression of estrogen and leptin receptors in a dose- and time-dependent manner. The effect of leptin on aromatase was direct and was mediated through the MAPK/Erk, STAT3 and PI3K pathways. The crosstalk between leptin and aromatase in the growth plate suggests that re-feeding during puberty may lead to increased estrogen level and activity, and consequently, irreversible premature epiphyseal growth plate closure. These results may have important implications for the development of novel treatment strategies for short stature in children. © 2018 Society for Endocrinology.

Aromatase Inhibitor-Induced Erythrocytosis in a Patient Undergoing Hormonal Treatment for Breast Cancer

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Sri Lakshmi Hyndavi Yeruva

2015-01-01

Full Text Available Aromatase inhibitors (AIs are most commonly used for breast cancer patients with hormone receptor positive disease. Although the side effect profile of aromatase inhibitors is well known, including common side effects like arthralgia, bone pain, arthritis, hot flashes, and more serious problems like osteoporosis, we present a case of an uncommon side effect of these medications. We report the case of a postmenopausal woman on adjuvant hormonal therapy with anastrozole after completing definitive therapy for stage IIIB estrogen receptor-positive breast cancer, who was referred to hematology service for evaluation of persistent erythrocytosis. Primary and known secondary causes of polycythemia were ruled out. On further evaluation, we found that her erythrocytosis began after initiation of anastrozole and resolved after it was discontinued. We discuss the pathophysiology of aromatase inhibitor-induced erythrocytosis and reference of similar cases reported in the literature.

Metabolism of 19-methyl-substituted steroids by human placental aromatase

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Beusen, D.D.; Carrell, H.L.; Covey, D.F.

1987-01-01

The 19-methyl analogues of androstenedione and its aromatization intermediates (19-hydroxyandrostenedione and 19-oxoandrostenedione) were evaluated as substrates of microsomal aromatase in order to determine the effect of a 19-alkyl substituent on the enzyme's regiospecificity. Neither the androstenedione analog [10-ethylestr-4-ene-3,17-dione (1c) nor the 19-oxoandrostenedione analog [10-acetylestr-4-ene-3,17-dione (3c)] was converted to estrogens or oxygenated metabolites by placental microsomes. In contrast, both analogues of 19-hydroxyandrostenedione [10-[(1S)-1-hydroxyethyl] extr-4-ene-3,17-dione (2c) and 10-[(1R)-1-hydroxyethyl]estr-4-ene-3,17-dione (2e)] were converted to the intermediate analog 3c in a process requiring O 2 and either NADH or NADPH. No change in enzyme regiospecificity was detected. The absolute configuration of 2e was determined by X-ray crystallography. Experiments with 18 O 2 established that 3c generated from 2c retained little 18 O ( 18 O (≅ 70%). All four 19-methyl steroids elicited type I difference spectra from placental microsomes in addition to acting as competitive inhibitors of aromatase. Pretreatment of microsomes with 4-hydroxyandrostenedione (a suicide inactivator of aromatase) abolished the metabolism of 2c and 2e to 3c, as well as the type I difference spectrum elicited by 2c and 2e. The failure of 2c, 2e, and 3c to undergo aromatization was rationalized in the context of a mechanistic proposal for the third oxygenation of aromatase requiring hydrogen abstraction at C 1 of 19,19-dihydroxyandrostenedione, homolytic cleavage of the C 10 -C 19 bond, and oxygen rebound at C 19

Which patients benefit most from adjuvant aromatase inhibitors?

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Viale, G; Regan, M M; Dell'Orto, P

2011-01-01

On average, aromatase inhibitors are better than tamoxifen when used as initial or sequential therapy for postmenopausal women with endocrine-responsive early breast cancer. Because there may be contraindications to their use based on side-effects or cost, we investigated subgroups in which aroma...

The interaction between aromatase, metalloproteinase 2,9 and cd44 in breast cancer A interação entre aromatase, metalloproteinase 2, 9 e cd44 no câncer de mama

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Fábio Bagnoli

2010-01-01

Full Text Available OBJECTIVE: This study intends to verify the expression levels and correlation of aromatase, matrix metalloproteinase 2 (MMP-2, matrix metalloproteinase 9 (MMP-9 and CD44 in ductal carcinoma in situ (DCIS and infiltrating ductal carcinoma (IDC when both are found in the same breast. METHODS: One hundred and ten cases were evaluated by tissue microarray (TMA and immunohistochemically screened with anti-aromatase polyclonal antibodies, anti-MMP-2 monoclonal antibodies, anti-MMP-9 policlonal antibodies and anti-CD44 monoclonal antibodies. RESULTS: Aromatase was expressed in IDC and DCIS in 63 (57.3% and 60 (67% of the cases respectively; MMP-2 was similarly expressed in IDC and DCIS in 15 (13.60% cases; MMP-9 was positively expressed in IDC and DCIS in 83 (75.50% and 82 (74.50% cases, respectively; CD44 was positively expressed in IDC and DCIS in 49 (44.50% and 48 (42.60% of the cases, respectively; all of them were highly correlated (pOBJETIVO: O objetivo desse estudo é verificar as expressões e correlações da aromatase, metalloproteinase 2 da matriz (MMP2, metalloproteinase 9 da matriz (MMP-9 e CD44 no carcinoma ductal in situ (CDIS e carcinoma ductal infiltrativo (CDI quando ambos estão presentes simultaneamente na mesma mama. MÉTODOS: Foram avaliados 110 casos pelo método de tissue microarray (TMA e através da utilização de anticorpos policlonais antiaromatase, anticorpos monoclonais anti-MMP-2, anticorpos policlonais anti-MMP-9 e anticorpos monoclonais anti-CD44. RESULTADOS: A aromatase estava expressa de forma positiva no CDI e CDIS em 63 (57,3% e 60 (67% casos, respectivamente. A expressão de MMP-2 estava expressa de forma positiva em 15 (13,6% casos tanto no CDI, quanto no CDIS. A expressão da MMP-9 estava expressa de forma positiva em 83 (75,5% e 82 (74,5% casos de CDI e CDIS, respectivamente. A expressão de CD44 estava expressa de forma positiva em 49 (44,5% e 48 (42,6% casos de CDI e CDIS, respectivamente. Todos eles

Plasma concentrations of estradiol and testosterone, gonadal aromatase activity and ultrastructure of the testis in Xenopus laevis exposed to estradiol or atrazine

International Nuclear Information System (INIS)

Hecker, Markus; Kim, Wan Jong; Park, June-Woo; Murphy, Margaret B.; Villeneuve, Daniel; Coady, Katherine K.; Jones, Paul D.; Solomon, Keith R.; Kraak, Glen van der; Carr, James A.; Smith, Ernest E.; Preez, Louis du; Kendall, Ronald J.; Giesy, John P.

2005-01-01

The ultrastructure of testicular cells of adult male African clawed frogs (Xenopus laevis) exposed to either estradiol (0.1 μg/L) or 2-chloro-4-ethylamino-6-isopropyl-amino-s-triazine (atrazine; 10 or 100 μg/L) was examined by electron microscopy and compared to plasma concentrations of the steroid hormones, testosterone (T) and estradiol (E2), testicular aromatase activity and gonad growth expressed as the gonado-somatic index (GSI). Exposure to E2 caused significant changes both at the sub-cellular and biochemical levels. Exposure to E2 resulted in significantly fewer sperm cells, inhibition of meiotic division of germ cells, more lipid droplets that are storage compartments for the sex steroid hormone precursor cholesterol, and lesser plasma T concentrations. Although not statistically significant, frogs exposed to E2 had slightly smaller GSI values. These results may be indicative of an inhibition of gonad growth and disrupted germ cell development by E2. Concentrations of E2 in plasma were greater in frogs exposed to E2 in water. Exposure to neither concentration of atrazine caused effects on germ cell development, testicular aromatase activity or plasma hormone concentrations. These results suggest that atrazine does not affect testicular function. In contrast, exposure of male X. laevis to E2 led to sub-cellular events that are indicative of disruption of testicular development, and demasculinization processes (decrease of androgen hormone titers). These results indicate that atrazine does not cause responses that are similar to those caused by exposure to E2

Modulation of Δ9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase

International Nuclear Information System (INIS)

Takeda, Shuso; Yamamoto, Ikuo; Watanabe, Kazuhito

2009-01-01

Δ 9 -Tetrahydrocannabinol (Δ 9 -THC), a major constituent of marijuana, has been shown to stimulate the growth of MCF-7 breast cancer cells through cannabinoid receptor-independent signaling [Takeda, S., Yamaori, S., Motoya, E., Matsunaga, T., Kimura, T., Yamamoto, I., Watanabe, K., 2008. Δ 9 -Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling. Toxicology 245, 141-146]. Although the growth of MCF-7 cells is known to be stimulated by 17β-estradiol (E 2 ), the interaction of Δ 9 -THC and E 2 in MCF-7 cell growth is not fully clarified so far. In the present study, by using E 2 -sensitive MCF-7 cells that have expressed cyclooxygenase-2 (COX-2) and cytochrome P450 19 (aromatase), we studied whether or not COX-2 and aromatase are involved in Δ 9 -THC-mediated MCF-7 cell proliferation. It was shown that Δ 9 -THC-induced MCF-7 cell growth was inhibited by COX-2 inhibitors and was stimulated by arachidonic acid (a COX substrate). However, the growth of MCF-7 cells induced by Δ 9 -THC was not stimulated by PGE 2 , and the expression of aromatase was not affected by COX-2 inhibitors, arachidonic acid, and PGE 2 , suggesting that there is a disconnection between COX-2 (PGE 2 ) and aromatase in Δ 9 -THC-mediated MCF-7 cell proliferation. On the other hand, Δ 9 -THC-induced MCF-7 cell growth was elevated by two kinds of aromatase inhibitors. Taken together with the evidence that Δ 9 -THC-induced MCF-7 cell proliferation was interfered with testosterone (an aromatase substrate) and exogenously provided E 2 , it is suggested that (1) the growth stimulatory effects of Δ 9 -THC are mediated by the product(s) of COX-2 except for PGE 2 , (2) the action of Δ 9 -THC is modulated by E 2 , and (3) COX-2 and aromatase are individually engaged in the proliferation of MCF-7 cells induced by Δ 9 -THC.

Neural stem cell sex dimorphism in aromatase (CYP19 expression: a basis for differential neural fate

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Jay Waldron

2010-11-01

Full Text Available Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Quebec, CanadaPurpose: Neural stem cell (NSC transplantation and pharmacologic activation of endogenous neurogenesis are two approaches that trigger a great deal of interest as brain repair strategies. However, the success rate of clinical attempts using stem cells to restore neurologic functions altered either after traumatic brain injury or as a consequence of neurodegenerative disease remains rather disappointing. This suggests that factors affecting the fate of grafted NSCs are largely understudied and remain to be characterized. We recently reported that aging differentially affects the neurogenic properties of male and female NSCs. Although the sex steroids androgens and estrogens participate in the regulation of neurogenesis, to our knowledge, research on how gender-based differences affect the capacity of NSCs to differentiate and condition their neural fate is lacking. In the present study, we explored further the role of cell sex as a determining factor of the neural fate followed by differentiating NSCs and its relationship with a potential differential expression of aromatase (CYP19, the testosterone-metabolizing enzyme.Results: Using NSCs isolated from the subventricular zone of three-month-old male and female Long-Evans rats and maintained as neurospheres, we showed that differentiation triggered by retinoic acid resulted in a neural phenotype that depends on cell sex. Differentiated male NSCs mainly expressed markers of neuronal fate, including ßIII-tubulin, microtubule associated protein 2, growth-associated protein 43, and doublecortin. In contrast, female NSCs essentially expressed the astrocyte marker glial fibrillary acidic protein. Quantification of the expression of aromatase showed a very low level of expression in undifferentiated female NSCs

Comparison of the effect of cortisol on aromatase activity and androgen metabolism in two human fibroblast cell lines derived from the same individual

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Svenstrup, B; Brünner, N; Dombernowsky, P

1990-01-01

The effect of preincubation with cortisol on estrogen and androgen metabolism was investigated in human fibroblast monolayers grown from biopsies of genital and non-genital skin of the same person. The activity in the cells of aromatase, 5 alpha-reductase, 17 beta-hydroxysteroid oxidoreductase.......5-1.0 x 10(-6) M in both cell lines. When preincubation with cortisol was omitted no estrogen synthesis was detected. The formation of androgen was not altered after preincubation with cortisol. Pronounced differences were found in estrogen and in androgen metabolism in the two cell lines suggesting...

Characterization of a cis-acting element involved in cell-specific expression of the zebrafish brain aromatase gene.

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Le Page, Yann; Menuet, Arnaud; Kah, Olivier; Pakdel, Farzad

2008-10-01

The cytochrome P450 Aromatase is the key enzyme catalyzing the conversion of androgens into estrogens. In zebrafish, the brain aromatase is encoded by cyp19b. Expression of cyp19b is restricted to radial glial cells bordering forebrain ventricles and is strongly stimulated by estrogens during development. At the promoter level, we have previously shown that an estrogen responsive element (ERE) is required for induction by estrogens. Here, we investigated the role of ERE flanking regions in the control of cell-specific expression. First, we show that a 20 bp length motif, named G x RE (glial x responsive element), acts in synergy with the ERE to mediate the estrogenic induction specifically in glial cells. Second, we demonstrate that, in vitro, this sequence binds factors exclusively present in glial or neuro-glial cells and is able to confer a glial specificity to an artificial estrogen-dependent gene. Taken together, these results contribute to the understanding of the molecular mechanisms allowing cyp19b regulation by estrogens and allowed to identify a promoter sequence involved in the strong estrogen inducibility of cyp19b which is specific for glial cells. The exceptional aromatase activity measured in the brain of teleost fish could rely on such mechanisms.

In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

International Nuclear Information System (INIS)

Lykkesfeldt, Anne E; Henriksen, Katrine L; Rasmussen, Birgitte B; Sasano, Hironobu; Evans, Dean B; Møller, Susanne; Ejlertsen, Bent; Mouridsen, Henning T

2009-01-01

New, third-generation aromatase inhibitors (AIs) have proven comparable or superior to the anti-estrogen tamoxifen for treatment of estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer. AIs suppress total body and intratumoral estrogen levels. It is unclear whether in situ carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved in the synthesis of aromatase, has been suggested as a surrogate marker for aromatase expression. Primary tumor material was retrospectively collected from 88 patients who participated in a randomized clinical trial comparing the AI letrozole to the anti-estrogen tamoxifen for first-line treatment of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate Wilcoxon analysis and the Cox-analysis were performed to evaluate time to progression (TTP) in relation to marker expression. Aromatase expression was associated with ER, but not with PR or COX-2 expression in carcinoma cells. Measurements of aromatase in WS were not comparable to results from TMAs. Expression of COX-2 and aromatase did not predict response to endocrine therapy. Aromatase in combination with high PR expression may select letrozole treated patients with a longer TTP. TMAs are not suitable for IHC analysis of in situ aromatase expression and we did not find COX-2 expression in carcinoma cells to be a surrogate marker for aromatase. In situ aromatase expression in tumor cells is associated with ER expression and may thus point towards good prognosis. Aromatase expression in cancer

Effect of dioxin exposure on aromatase expression in ovariectomized rats

International Nuclear Information System (INIS)

Ye Lan; Leung, Lai K.

2008-01-01

Because of their persistence in the environment dioxins are one of the most concerned classes of carcinogens. Displaying both pro- and anti-agonistic properties to some hormone receptors, the pollutants are also known to be endocrine disruptors. Humans can be exposed to this pollutant through contaminated food, air, drinking water, etc. The female hormone estrogen may initiate various physiological functions, and excessive exposure to this hormone is a documented risk factor for carcinogenesis. Cyp19 (aromatase) catalyses the last step of estrogen biosynthesis, while cyp1a1 can hydroxylate and deactivate the hormone. In the present study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) on aromatase expression in the brain and adipose tissue in ovariectomized Sprague Dawley rats. Female rats were given 2.5 μg/kg TCDD p.o. before and after ovariectomy. Real-time PCR and western blot analysis indicated that pre-ovariectomy administration of TCDD could significantly reduce aromatase expression in the brain but increase the expression in the adipose tissue. In addition, increased plasma estrogen level and uterine weight were observed in these rats. These parameters did not change in rats with post-ovariectomy TCDD treatment. Our results suggested that the timing of exposure to the toxicant could determine the estrogenicity of TCDD. No correlation between cyp1a1 and cyp19 expression was observed

Brain aromatase (Cyp19A2) and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis: Neuroanatomical and functional relations

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Strobl-Mazzulla, P. H.; Lethimonier, C.; Gueguen, M.M.; Karube, M.; Fernandino, J.I.; Yoshizaki, G.; Patino, R.; Strussmann, C.A.; Kah, O.; Somoza, G.M.

2008-01-01

Although estrogens exert many functions on vertebrate brains, there is little information on the relationship between brain aromatase and estrogen receptors. Here, we report the cloning and characterization of two estrogen receptors, ?? and ??, in pejerrey. Both receptors' mRNAs largely overlap and were predominantly expressed in the brain, pituitary, liver, and gonads. Also brain aromatase and estrogen receptors were up-regulated in the brain of estradiol-treated males. In situ hybridization was performed to study in more detail, the distribution of the two receptors in comparison with brain aromatase mRNA in the brain of adult pejerrey. The estrogen receptors' mRNAs exhibited distinct but partially overlapping patterns of expression in the preoptic area and the mediobasal hypothalamus, as well as in the pituitary gland. Moreover, the estrogen receptor ??, but not ??, were found to be expressed in cells lining the preoptic recess, similarly as observed for brain aromatase. Finally, it was shown that the onset expression of brain aromatase and both estrogen receptors in the head of larvae preceded the morphological differentiation of the gonads. Because pejerrey sex differentiation is strongly influenced by temperature, brain aromatase expression was measured during the temperature-sensitive window and was found to be significantly higher at male-promoting temperature. Taken together these results suggest close neuroanatomical and functional relationships between brain aromatase and estrogen receptors, probably involved in the sexual differentiation of the brain and raising interesting questions on the origin (central or peripheral) of the brain aromatase substrate. ?? 2008 Elsevier Inc.

3D-QSAR Study of Steroidal and Azaheterocyclic Human Aromatase Inhibitors using Quantitative Profile of Protein-Ligand Interactions

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Aromatase is a member of the cytochrome P450 superfamily responsible for a key step in the biosynthesis of estrogens. As estrogens are involved in the control of important reproduction-related processes, including sexual differentiation and maturation, aromatase is a potential ta...

Comprehensive and Automated Linear Interaction Energy Based Binding-Affinity Prediction for Multifarious Cytochrome P450 Aromatase Inhibitors

NARCIS (Netherlands)

van Dijk, Marc; Ter Laak, Antonius M; Wichard, Jörg D; Capoferri, Luigi; Vermeulen, Nico P E; Geerke, Daan P

2017-01-01

Cytochrome P450 aromatase (CYP19A1) plays a key role in the development of estrogen dependent breast cancer, and aromatase inhibitors have been at the front line of treatment for the past three decades. The development of potent, selective and safer inhibitors is ongoing with in silico screening

New Insights Into the Role of Estrogens in Male Fertility Based on Findings in Aromatase-Deficient Zebrafish.

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Tang, Haipei; Chen, Yu; Liu, Yun; Yin, Yike; Li, Gaofei; Guo, Yin; Liu, Xiaochun; Lin, Haoran

2017-09-01

It has been demonstrated that estrogens are indispensable for male fertility in mammals. Aromatase (encoded by CYP19) catalyzes the final step of estradiol biosynthesis. However, less is known about the role of aromatase in male fertility in nonmammalian species. Fish aromatase is encoded by two separate genes: the gonad-specific cyp19a1a and the brain-specific cyp19a1b. In a recent study, we used transcription activatorlike effector nucleases to systematically generate cyp19a1a and cyp19a1b mutant lines and a cyp19a1a;cyp19a1b double-mutant line in zebrafish and demonstrated that cyp19a1a was indispensable for sex differentiation. In this study, we focused on male fertility in these aromatase-deficient zebrafish. Our results showed that all aromatase-deficient male fish had normal fertility even at 1 year after fertilization. Interestingly, we observed more spermatozoa in the cyp19a1a and double-mutant males than in the wild-type and cyp19a1b mutant males. The whole-body androgen levels, follicle-stimulating hormone β and luteinizing hormone β protein levels in the pituitary, and transcript levels of genes known to be involved in spermatogenesis and steroidogenesis in the testes were significantly higher in the cyp19a1a mutant and aromatase double-mutant males than in the wild-type and cyp19a1b mutant males. These results might explain why more spermatozoa were observed in these fish. Collectively, our findings indicate that estrogens are not needed to achieve and maintain normal fertility in male zebrafish. This finding challenges the traditional view that estrogens are indispensable for male fertility. Copyright © 2017 Endocrine Society.

Molecular cloning of P450 aromatase from the leopard gecko and its expression in the ovary.

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Endo, Daisuke; Park, Min Kyun

2005-07-01

In this study, we identified the cDNA of P450 aromatase in the leopard gecko, a lizard with temperature-dependent sex determination. The cDNA encodes a putative protein of 505 amino acids. The deduced amino acid sequence of leopard gecko aromatase cDNA showed 80% identity with that of turtles, 70% with humans and 77% with chickens. This is the first report of the identification of P450 aromatase cDNA in squamata species. It has been reported that this gene is expressed in different layers of cells in the ovary of mammalian species and avian species. Thus, we also investigated cells expressing the mRNA of this gene in the ovary of the leopard gecko by RT-PCR and in situ hybridization. The mRNA expression of leopard gecko P450 aromatase was localized in both the thecal and granulosa cell layers in the ovary. The expression in thecal and granulosa cell layers was examined in the largest follicle, second largest follicle and third largest follicle by RT-PCR. A higher level of mRNA expression was observed in the granulosa cell layer of the second largest follicle than in other cell layers. This result may reflect the characteristics of follicles in species with automonochronic ovulation.

Potential contribution of aromatase inhibition to the effects of nicotine and related compounds on the brain

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Anat eBiegon

2012-11-01

Full Text Available Cigarette smoking continues to be a major public health problem, and while smoking rates in men have shown some decrease over the last few decades, smoking rates among girls and young women are increasing. Practically all of the important aspects of cigarette smoking are sexually dimorphic. Women become addicted more easily than men, while finding it harder to quit. Nicotine replacement appears to be less effective in women. This may be linked to the observation that women are more sensitive than men to non-nicotine cues or ingredients in cigarettes. The reasons for these sex differences are mostly unknown. Several lines of evidence suggest that many of the reported sex differences related to cigarette smoking may stem from the inhibitory effects of nicotine and other tobacco alkaloids on estrogen synthesis via the enzyme aromatase (cyp19a gene product. Aromatase is the last enzyme in estrogen biosynthesis, catalyzing the conversion of androgens to estrogens. This review provides a summary of experimental evidence supporting brain aromatase as a potential mediator and/or modulator of nicotine actions in the brain, contributing to sex differences in smoking behavior. Additional research on the interaction between tobacco smoke, nicotine and aromatase may help devise new, sex specific methods for prevention and treatment of smoking addiction.

Effect of β-agonist on the dexamethasone-induced expression of aromatase by the human monocyte cells

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Masatada Watanabe

2017-02-01

Full Text Available Emerging evidence suggests that sex steroids are important for human skin health. In particular, estrogen improves skin thickness, elasticity and moisture of older women. The major source of circulating estrogen is the ovary; however, local estrogen synthesis and secretion have important roles in, for example, bone metabolism and breast cancer development. We hypothesized that infiltrated peripheral monocytes are one of the sources of estrogen in skin tissues. We also hypothesized that, during atopic dermatitis under stress, a decline in the hypothalamus–pituitary–adrenal axis (HPA and facilitation of the (hypothalamus–sympathetic–adrenomedullary system (SAM attenuates estrogen secretion from monocytes. Based on this hypothesis, we tested aromatase expression in the human peripheral monocyte-derived cell line THP-1 in response to the synthetic glucocorticoid dexamethasone (Dex, the synthetic β-agonist isoproterenol (Iso and the β-antagonist propranolol (Pro. Dex mimics glucocorticoid secreted during excitation of the HPA, and Iso mimics catecholamine secreted during excitation of the SAM. We found that aromatase activity and the CYP19A1 gene transcript were both upregulated in THP-1 cells in the presence of Dex. Addition of Iso induced their downregulation and further addition of Pro rescued aromatase expression. These results may suggest that attenuation of estrogen secretion from peripheral monocytes could be a part of the pathology of stress-caused deterioration of atopic dermatitis. Further examination using an in vitro human skin model including THP-1 cells might be a valuable tool for investigating the therapeutic efficacy and mechanism of estrogen treatment for skin health.

Pharmacogenetics and aromatase inhibitor induced side effects in breast cancer patients.

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Sini, Valentina; Botticelli, Andrea; Lunardi, Gianluigi; Gori, Stefania; Marchetti, Paolo

2017-06-01

This paper reviews genetic variations mainly related to the onset of adverse events during aromatase inhibitors in early breast cancer. Genetic variability could occur at different steps. The analysis included studies that involved breast cancer patients, treated with an aromatase inhibitor, genotyped for CYP19A1 and/or CYP17A1 and/or CYP27B1 and/or TCLA1, and/or RANK/RANKL/OPG and/or ESR1/ESR2, and assessed for toxicity profile. Twenty-two articles were included for the analysis. Three studies evaluated outcomes and adverse events; 19 studies assessed only side effects. Functional variations may be useful in predicting the onset of toxicities. The identification of polymorphisms at increased risk of toxicity may enable patient management. However, more data are needed to be applied in the individualization of treatment in daily practice.

Managing arthralgia in a postmenopausal woman taking an aromatase inhibitor for hormonesensitive early breast cancer: a case study

International Nuclear Information System (INIS)

Bryce, Jane; Bauer, Martina; Hadji, Peyman

2012-01-01

In order to reduce the risk of recurrence, adjuvant treatment with an aromatase inhibitor (AI) is recommended for postmenopausal women following surgery for hormone receptor-positive breast cancer. AIs are associated with improved disease-free survival compared with tamoxifen. The adverse events associated with AIs resemble those of menopause, such as bone density loss and musculoskeletal symptoms. We examine the case of a postmenopausal woman who was prescribed anastrozole, a nonsteroidal AI, as adjuvant therapy following surgery for estrogen and progesterone receptor-positive (ER and PgR+) breast cancer. A 58-year-old postmenopausal woman diagnosed with ER and PgR+ breast cancer was prescribed anastrozole as adjuvant therapy following a right-inferior quadrantectomy. After experiencing joint pain and stiffness, she was prescribed paracetamol and a topical nonsteroidal anti-inflammatory drug. She was also counseled on nonpharmacological interventions. However, she continued to experience symptoms, and reported that she was not taking anastrozole regularly. The case study patient ultimately found relief by switching to letrozole, another aromatase inhibitor. This approach is supported by recent studies examining the benefits of switching strategies between aromatase inhibitors in order to relieve symptoms of arthralgia/myalgia. Both adherence and strategies for managing aromatase inhibitor-associated arthralgia are key to deriving maximal clinical benefit from AI therapy. Switching from one aromatase inhibitor to another may provide a viable option in managing adverse events and enhancing adherence to medication

Aromatase inhibitors in the treatment of deep endometriosis

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Simone Ferrero

2009-09-01

Full Text Available Recent case reports and pilot studies suggested that aromatase inhibitors might be effective in treating pain symptoms related to the presence of endometriosis. We present the case of a 32-year-old woman who suffered dysmenorrhea, dyspareunia, chronic pelvic pain, and dyschezia caused by rectovaginal endometriosis. Pain symptoms recurred after treatment with the oral contraceptive pill; the patient refused surgery. Therefore a double-drug regimen including letrozole (2.5 mg/day and norethisterone acetate (2.5 mg/day was offered to the patient. The scheduled length of treatment was six months. This double-drug regimen determined a quick and significant improvement in all pain symptoms. During treatment, the patient complained mild arthralgia. After the interruption of treatment, pain symptoms quickly recurred and at 6-month follow-up their intensity was similar to baseline values. Operative laparoscopy was performed, the presence of rectovaginal endometriosis was confirmed and all visible endometriotic lesions were excised. Aromatase inhibitors might be offered when pain symptoms caused by endometriosis persist during the administration of other hormonal therapies and the patient refuses surgery. However, women must be informed that these drugs determine only a temporary relief of pain symptoms and might cause adverse effects (such as arthralgia.

Dietary administration of the licorice flavonoid isoliquiritigenin deters the growth of MCF-7 cells overexpressing aromatase.

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Ye, Lan; Gho, Wai M; Chan, Franky L; Chen, Shiuan; Leung, Lai K

2009-03-01

Licorice is the sweet-tasting rhizomes of a bean plant and is quite commonly used in Western countries for culinary purposes, while it is a medicinal herb in China. Many flavonoids have been isolated from licorice, and their pharmacological properties may be applicable in preventive medicine. Overexposure to estrogen has been implicated in the etiology of breast cancer, and cytochrome P450 (CYP) 19 enzyme, or aromatase, catalyzes the rate-limiting reaction. Phytocompounds that are able to inhibit this enzyme may potentially suppress breast cancer development. In the present study the licorice flavonoid isoliquiritigenin (ILN) was shown to be an aromatase inhibitor in recombinant protein and MCF-7 cells stably transfected with CYP19 (MCF-7aro). ILN displayed a K(i) value of around 3 muM, and it also blocked the MCF-7aro cell growth pertaining to the enzyme activity in vitro. Subsequently, the compound administered in diet was given to ovariectomized athymic mice transplanted with MCF-7aro cells. This mouse model is widely accepted for studying postmenopausal breast cancer. The phytochemical significantly deterred the xenograft growth without affecting the body weight. Subsequently, the flavonoid's effect on CYP19 transcriptional control in vitro was also investigated. At the mRNA level, ILN could also suppress the expression in wild-type MCF-7 cells. Reporter gene assay and real-time PCR verified that the transactivity of CYP19 driven by promoters I.3 and II was suppressed in these cells. Deactivation of C/EBP could be the underlying molecular mechanism. Our study demonstrated that ILN was an inhibitor of aromatase and a potential chemopreventive agent against breast cancer.

Polymerase chain reaction amplification fails to detect aromatase cytochrome P450 transcripts in normal human endometrium or decidua.

Science.gov (United States)

Bulun, S E; Mahendroo, M S; Simpson, E R

1993-06-01

It has been proposed that the biosynthesis of estrogens by the human endometrium may be of physiological significance during the menstrual cycle. Local estrogen production was also suggested to be important in the development of endometrial cancer; however, the presence or absence of aromatase enzyme activity in normal human endometrium is controversial. To address this issue, we used a sensitive technique capable of detecting mRNA transcripts present in only very low copy number. The polymerase chain reaction linked to reverse transcription (RT-PCR) was used to evaluate the presence or absence of aromatase cytochrome P450 (P450arom) transcripts in endometrial tissues (n = 7) and endometrial stromal cells (n = 9) under various culture conditions. RNA was isolated from four proliferative and three secretory tissue samples and from cultured endometrial stromal cells isolated from seven proliferative and two secretory endometria. Five sets of cultures were treated with medroxyprogesterone acetate (MPA), estradiol (E2), and forskolin. Additionally, RNA was isolated from decidualized endometrium obtained from a patient with tubal pregnancy. A single stranded cDNA was synthesized from total RNA using Moloney murine leukemia virus reverse transcriptase and a P450arom-specific oligonucleotide. The single stranded cDNA was used as a template for PCR and was amplified for 20-35 cycles using P450arom-specific primers. RNA from adipose tissue and placenta was amplified to provide positive controls, whereas myometrial RNA was used as a negative control. In two experiments involving two endometrial tissues and three sets of cells in culture, a rat P450arom cRNA was coamplified in each sample as an internal control to demonstrate that the remote possibility of RT-PCR failures in individual test samples cannot account for our negative results. By Southern or slot blot hybridization of the amplified fragments using human and rat P450arom-specific probes, we found no evidence for

In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

DEFF Research Database (Denmark)

Lykkesfeldt, Anne E; Henriksen, Katrine L; Rasmussen, Birgitte B

2009-01-01

BACKGROUND: New, third-generation aromatase inhibitors (AIs) have proven comparable or superior to the anti-estrogen tamoxifen for treatment of estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer. AIs suppress total body and intratumoral estrogen levels. It is unclear...... whether in situ carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved...... of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate...

Estrogen receptor-independent catechol estrogen binding activity: protein binding studies in wild-type, Estrogen receptor-alpha KO, and aromatase KO mice tissues.

Science.gov (United States)

Philips, Brian J; Ansell, Pete J; Newton, Leslie G; Harada, Nobuhiro; Honda, Shin-Ichiro; Ganjam, Venkataseshu K; Rottinghaus, George E; Welshons, Wade V; Lubahn, Dennis B

2004-06-01

Primary evidence for novel estrogen signaling pathways is based upon well-documented estrogenic responses not inhibited by estrogen receptor antagonists. In addition to 17beta-E2, the catechol estrogen 4-hydroxyestradiol (4OHE2) has been shown to elicit biological responses independent of classical estrogen receptors in estrogen receptor-alpha knockout (ERalphaKO) mice. Consequently, our research was designed to biochemically characterize the protein(s) that could be mediating the biological effects of catechol estrogens using enzymatically synthesized, radiolabeled 4-hydroxyestrone (4OHE1) and 4OHE2. Scatchard analyses identified a single class of high-affinity (K(d) approximately 1.6 nM), saturable cytosolic binding sites in several ERalphaKO estrogen-responsive tissues. Specific catechol estrogen binding was competitively inhibited by unlabeled catechol estrogens, but not by 17beta-E2 or the estrogen receptor antagonist ICI 182,780. Tissue distribution studies indicated significant binding differences both within and among various tissues in wild-type, ERalphaKO, and aromatase knockout female mice. Ligand metabolism experiments revealed extensive metabolism of labeled catechol estrogen, suggesting that catechol estrogen metabolites were responsible for the specific binding. Collectively, our data provide compelling evidence for the interaction of catechol estrogen metabolites with a novel binding protein that exhibits high affinity, specificity, and selective tissue distribution. The extensive biochemical characterization of this binding protein indicates that this protein may be a receptor, and thus may mediate ERalpha/beta-independent effects of catechol estrogens and their metabolites.

The ovine sexually dimorphic nucleus, aromatase, and sexual partner preferences in sheep.

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Roselli, C E; Stormshak, F

2010-02-28

We are using the domestic ram as an experimental model to examine the role of aromatase in the development of sexual partner preferences. This interest has arisen because of the observation that as many as 8% of domestic rams are sexually attracted to other rams (male-oriented) in contrast to the majority of rams that are attracted to estrous ewes (female-oriented). Our findings demonstrate that aromatase expression is enriched in a cluster of neurons in the medial preoptic nucleus called the ovine sexually dimorphic nucleus (oSDN). The size of the oSDN is associated with a ram's sexual partner preference, such that the nucleus is 2-3 times larger in rams that are attracted to females (female-oriented) than in rams that are attracted to other rams (male-oriented). Moreover, the volume of the oSDN in male-oriented rams is similar to the volume in ewes. These volume differences are not influenced by adult concentrations of serum testosterone. Instead, we found that the oSDN is already present in late gestation lamb fetuses (approximately day 135 of gestation) when it is approximately 2-fold greater in males than in females. Exposure of genetic female fetuses to exogenous testosterone during the critical period for sexual differentiation masculinizes oSDN volume and aromatase expression when examined subsequently on day 135. The demonstration that the oSDN is organized prenatally by testosterone exposure suggests that the brain of the male-oriented ram may be under-androgenized during development. Copyright 2009 Elsevier Ltd. All rights reserved.

Gonadal expression of aromatase and estrogen receptor alpha genes in two races of Tunisian mice and their hypofertile hybrids.

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Saïd, Lamia; Delalande, Christelle; Britton-Davidian, Janice; Saïd, Khaled; Saad, Ali; Carreau, Serge

2007-07-01

House mice (Mus musculus domesticus) in Tunisia consists of two races, one carries the 40-acrocentric standard karyotypes and the other one is a robertsonian race (2n=22) homozygous for nine centric fusions (Rb). The F1 hybrids between the two chromosomal races showed a significant decrease in reproductive success and litter size. Such results can be related to the formation of meiotic trivalent in the hybrids leading to the production of viable aneuploid gametes and post-zygotic elimination of embryos due to chromosomal non disjunction events at meiosis. Moreover, testicular histology of F1 and backcross males showed in some cases a breakdown in spermatogenesis. In both females and males, androgens but also estrogens play an important role in gametogenesis. In this study, we have studied aromatase and estrogen receptor alpha (ERalpha) gene expression in the gonads of the two parental races and their chromosomal hybrids. The results showed that aromatase and ERalpha mRNAs are expressed in hybrid males of inter-racial crosses (female22Rb x male40Std and female40Std x male22Rb) and in hybrid females of inter-racial crosses (female22Rb x male40Std) as in the two parental races. However, in hybrid females of inter-racial crosses (female40Std x male22Rb) the amount of aromatase transcripts decreased sharply suggesting that this gene is involved in the breakdown of hybrid fertility in females, but not in males. However, in hybrid males, a putative post-translational modification of this enzyme, in terms of activity, should be verified.

Comparing exercise responses to aerobic plus resistance training between postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy and healthy women.

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Paulo, Thais R S de; Winters-Stone, Kerri M; Viezel, Juliana; Rossi, Fabricio E; Aro, Bruna L; Trindade, Ana Carolina A C; Codogno, Jamile S; Freitas Junior, Ismael F

2018-04-12

The aim of this study was to explore whether postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy differ from healthy postmenopausal women in their response to the same aerobic + resistance training. The participants were separated into two groups: postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy for an average of 20 months (18 women) and healthy postmenopausal women (24 women). We assessed aerobic capacity (predicted maximum oxygen uptake (VO 2 max) and maximum running velocity test (Vmax)) through a walking test, upper and lower body muscle strength using an estimated one-repetition maximum test, and body composition by dual-energy X-ray absorptiometry at baseline and at three, six, and nine months, respectively. The exercise program was performed three times/week over nine months and consisted of 40 min of machine-based strength training (seated cable row, bench press, leg extension, leg press, and leg curl, as well as bridge, abdominal, and standard plank exercises) followed by 30 min of treadmill walking. Analysis of variance (ANOVA) with repeated measures was used to compare the groups over time. Postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy and healthy postmenopausal women presented similar improvements in estimated lower body strength, predicted VO 2max and V max , and body fat mass. For maximal upper body strength, there was a significant group x time interaction after six months of training (p = 0.01). The healthy postmenopausal women presented a significant increase in upper body strength after six months, while postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy demonstrated an improvement only at nine months of training. The breast cancer survivors undergoing aromatase inhibitor therapy presented increased lean mass while healthy postmenopausal women maintained values over time (Breast cancer: 33.7 ± 3.9(Pre) vs. 34.1�

Potential role of aromatase inhibitors in the treatment of endometriosis

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Abu Hashim H

2014-07-01

Full Text Available Hatem Abu HashimDepartment of Obstetrics and Gynecology, Faculty of Medicine, Mansoura University, Mansoura, EgyptAbstract: Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5%–10% of reproductive-age women, with a prevalence of 5%–50% in infertile women and >33% of women with chronic pelvic pain. Third-generation aromatase inhibitors (AIs are approved adjuvants for the treatment of estrogen receptor-positive breast cancer. Molecular studies have revealed the presence of aromatase P450, the key enzyme in the biosynthesis of ovarian estradiol, inside the endometriotic tissue, indicating local synthesis of estradiol. Thereby, AIs represent an appealing medical option for the management of different aspects of this enigmatic disease, especially pelvic pain and infertility. Accordingly, this review aims to evaluate the potential role of AIs in the treatment of endometriosis-associated symptoms, mainly pain and infertility. Notably, several studies have demonstrated that the combination of AIs with conventional therapy as oral contraceptive pills, progestins, or gonadotropin-releasing hormone analogs can be used to control endometriosis-associated pain and pain recurrence in premenopausal women, particularly those with pain due to rectovaginal endometriosis refractory to other medical or surgical treatment. Some case reports have shown promising results in the treatment of postmenopausal endometriosis as first-line treatment, when surgery is contraindicated, or as second-line treatment in the case of postoperative recurrence. Third-generation AIs, especially letrozole, have challenged clomiphene citrate as an ovulation-induction agent in patients with polycystic ovary syndrome and in cases of unexplained infertility. However, few studies are available regarding the use of AIs to treat endometriosis-associated infertility. Therefore, larger multicenter randomized trials using AIs for the treatment of endometriosis

Analysis of Obesity-Related Factors and their Association with Aromatase Expression in Canine Malignant Mammary Tumours.

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Shin, J-I; Lim, H-Y; Kim, H-W; Seung, B-J; Ju, J-H; Sur, J-H

2016-07-01

This study was designed to investigate the role of obesity in canine malignant mammary tumours (CMMTs), by assessing aromatase expression and the regulatory roles of immune mediators such as cyclo-oxygenase-2 (COX2), prostaglandin E2 (PGE2), nuclear factor kappa beta (NF-κB), hypoxia inducible factor-1α (HIF-1α) and adipokines (i.e. leptin) in lean, optimal body weight, overweight and obese animals. Clinicopathological data, including the breed, body weight, body condition score and age and neutering status, were collected, together with histopathological characteristics (i.e. histological types, grading and lymphatic invasion). To determine the expression of each factor, immunohistochemistry was conducted with 60 samples of malignant CMMTs. CMMTs from overweight and obese animals had significantly elevated levels of PGE2, and aromatase expression correlated significantly with PGE2, NF-κB and leptin expression. However, no significant difference was observed in terms of histopathological characteristics. The results suggest that PGE2, a known obesity-related immune mediator, could be upregulated in CMMTs from overweight and obese animals. In addition, PGE2, NF-κB and leptin influenced the expression of aromatase, as observed in women. Copyright © 2016 Elsevier Ltd. All rights reserved.

Disruptions in aromatase expression in the brain, reproductive behavior, and secondary sexual characteristics in male guppies (Poecilia reticulata) induced by tributyltin.

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Tian, Hua; Wu, Peng; Wang, Wei; Ru, Shaoguo

2015-05-01

Although bioaccumulation of tributyltin (TBT) in fish has been confirmed, information on possible effects of TBT on reproductive system of fish is still relatively scarce, particularly at environmentally relevant levels. To evaluate the adverse effects and intrinsic toxicological properties of TBT in male fish, we studied aromatase gene expression in the brain, sex steroid contents, primary and secondary sexual characteristics, and reproductive behavior in male guppies (Poecilia reticulata) exposed to tributyltin chloride at the nominal concentrations of 5, 50, and 500 ng/L for 28 days in a semi-static exposure system. Radioimmunoassay demonstrated that treatment with 50 ng/L TBT caused an increase in systemic levels of testosterone of male guppies. Gonopodial index, which showed a positive correlation with testosterone levels, was elevated in the 5 ng/L and 50 ng/L TBT treated groups. Real-time PCR revealed that TBT exposure had inhibiting effects on expression of two isoforms of guppy aromatase in the brain, and these changes at the molecular levels were associated with a disturbance of reproductive behavior of the individuals, as measured by decreases in frequencies of posturing, sigmoid display, and chase activities when males were paired with females. This study provides the first evidence that TBT can cause abnormalities of secondary sexual characteristics in teleosts and that suppression of reproductive behavior in teleosts by TBT is due to its endocrine-disrupting action as an aromatase inhibitor targeting the nervous system. Copyright © 2015 Elsevier B.V. All rights reserved.

Paternal Retrieval Behavior Regulated by Brain Estrogen Synthetase (Aromatase) in Mouse Sires that Engage in Communicative Interactions with Pairmates.

Science.gov (United States)

Akther, Shirin; Huang, Zhiqi; Liang, Mingkun; Zhong, Jing; Fakhrul, Azam A K M; Yuhi, Teruko; Lopatina, Olga; Salmina, Alla B; Yokoyama, Shigeru; Higashida, Chiharu; Tsuji, Takahiro; Matsuo, Mie; Higashida, Haruhiro

2015-01-01

Parental behaviors involve complex social recognition and memory processes and interactive behavior with children that can greatly facilitate healthy human family life. Fathers play a substantial role in child care in a small but significant number of mammals, including humans. However, the brain mechanism that controls male parental behavior is much less understood than that controlling female parental behavior. Fathers of non-monogamous laboratory ICR mice are an interesting model for examining the factors that influence paternal responsiveness because sires can exhibit maternal-like parental care (retrieval of pups) when separated from their pups along with their pairmates because of olfactory and auditory signals from the dams. Here we tested whether paternal behavior is related to femininity by the aromatization of testosterone. For this purpose, we measured the immunoreactivity of aromatase [cytochrome P450 family 19 (CYP19)], which synthesizes estrogen from androgen, in nine brain regions of the sire. We observed higher levels of aromatase expression in these areas of the sire brain when they engaged in communicative interactions with dams in separate cages. Interestingly, the number of nuclei with aromatase immunoreactivity in sires left together with maternal mates in the home cage after pup-removing was significantly larger than that in sires housed with a whole family. The capacity of sires to retrieve pups was increased following a period of 5 days spent with the pups as a whole family after parturition, whereas the acquisition of this ability was suppressed in sires treated daily with an aromatase inhibitor. The results demonstrate that the dam significantly stimulates aromatase in the male brain and that the presence of the pups has an inhibitory effect on this increase. These results also suggest that brain aromatization regulates the initiation, development, and maintenance of paternal behavior in the ICR male mice.

Successful treatment of low-grade endometrial cancer in premenopausal women with an aromatase inhibitor after failure with oral or intrauterine progesterone

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Alli Straubhar

2017-08-01

Full Text Available Introduction: Young women with endometrial intraepithelial hyperplasia or low-grade endometrial carcinoma are potential candidates for conservative fertility sparing therapy utilizing progesterone rather than hysterectomy. High-dose progesterone treatment is associated with 55–80% initial response but high relapse rates. Using aromatase inhibitors in conjunction with high-dose progesterone has largely been unstudied. Case descriptions: Three obese premenopausal women with endometrial cancer failed to respond to oral or intrauterine progesterone as first line therapy. Due to their desire to continue to pursue fertility sparing treatment options, an aromatase inhibitor was added to their treatment regimen. This resulted in resolution of their malignancy in each case. Discussion: In obese premenopausal women, the mechanism of malignant transformation in endometrial carcinoma is considered to be an association with relatively high levels of serum estrogen from peripheral conversion of androgens to estrone in adipose tissue with a deficiency in progesterone exposure due to chronic anovulation. Using aromatase inhibitors seems reasonable as an adjunct to progesterone given the high likelihood that this population has a significant proportion of their estrogen production coming from peripheral conversion in adipose tissue. This case series is unique in that each woman initially failed to respond to progesterone but had resolution when an aromatase inhibitor was added to their treatment regimen. This would suggest that obese women with low grade malignancy or hyperplasia who have no radiographic evidence of deep myometrial invasion, ovarian or retroperitoneal metastases and who wish to retain their fertility may be treated with intrauterine progesterone and an aromatase inhibitor.

Synthesis and evaluation of a dimer of 2-(4-pyridylmethyl)-1-indanone as a novel nonsteroidal aromatase inhibitor.

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Gupta, Ranju; Jindal, Dharam Paul; Jit, Birinder; Narang, Gaurav; Palusczak, Anja; Hartmann, Rolf W

2004-07-01

A novel dimer of 2-(4-pyridylmethyl)-1-indanone (2) was obtained while carrying out aldol condensation of 1-indanone with pyridine-4-carboxaldehyde in potassium hydroxide. The structure of dimer 3 has been established using various spectral techniques and was screened for its ability to inhibit the cytochrome P(450) enzyme aromatase. The dimer showed strong inhibition of human placental aromatase and was found 3 times more potent (RP = 3, IC(50) = 10.2 microM) as compared to aminoglutethimide (RP = 1, IC(50) = 18.5 microM.

Brain and gonadal aromatase activity and steroid hormone levels in female and polymorphic males of the peacock blenny Salaria pavo.

Science.gov (United States)

Gonçalves, David; Teles, Magda; Alpedrinha, João; Oliveira, Rui F

2008-11-01

In the peacock blenny Salaria pavo large males with well-developed secondary sexual characters establish nests and attract females while small "sneaker" males mimic female sexual displays in order to approach the nests of larger males and parasitically fertilize eggs. These alternative reproductive tactics are sequential, as sneakers irreversibly switch into nesting males. This transition involves major morphologic and behavioral changes and is likely to be mediated by hormones. This study focuses on the role of aromatase, an enzyme that catalyses the conversion of androgens into estrogens, in the regulation of male sexual polymorphism in S. pavo. For this, sex steroid plasma levels and aromatase activity (AA) in gonads, whole brain and brain macroareas were determined in sneakers, transitional males (i.e. sneakers undergoing the transition into nesting males), nesting males and females collected in the field. AA was much higher in ovarian tissue than in testicular tissue and accordingly circulating estradiol levels were highest in females. This supports the view that elevated AA and estradiol levels are associated with the development of a functional ovary. Transitional males are in a non-reproductive phase and had underdeveloped testes when compared with sneakers and nesting males. Testicular AA was approximately 10 times higher in transitional males when compared with sneakers and nesting males, suggesting high AA has a suppressive effect on testicular development. Nesting males had significantly higher plasma levels of both testosterone (T) and 11-ketotestosterone when compared with the other male morphs and previous studies demonstrated that these androgens suppress female-like displays in sneakers. In the brain, AA was highest in macroareas presumably containing hypothalamic nuclei traditionally associated with the regulation of reproductive behaviors. Overall, females presented the highest levels of brain AA. In male morphs AA increased from sneakers, to

Direct Regulation of Aromatase B Expression by 17β-Estradiol and Dopamine D1 Receptor Agonist in Adult Radial Glial Cells

OpenAIRE

Xing, Lei; Esau, Crystal; Trudeau, Vance L.

2016-01-01

Aromatase cytochrome P450arom (cyp19) is the only enzyme that has the ability to convert androgens into estrogens. Estrogens, which are produced locally in the vertebrate brain play many fundamental roles in neuroendocrine functions, reproductive functions, socio-sexual behaviors, and neurogenesis. Radial glial cells (RGCs) are neuronal progenitor cells that are abundant in fish brains and are the exclusive site of aromatase B expression and neuroestrogen synthesis. Using a novel in vitro RGC...

Anti-angiogenic activity in metastasis of human breast cancer cells irradiated by a proton beam

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyu-Shik; Shin, Jin-Sun; Nam, Kyung-Soo [Dongguk University, Gyeongju (Korea, Republic of); Shon, Yun-Hee [Kyungpook National University Hospital, Daegu (Korea, Republic of)

2012-07-15

Angiogenesis is an essential process of metastasis in human breast cancer. We investigated the effects of proton beam irradiation on angiogenic enzyme activities and their expressions in MCF-7 human breast cancer cells. The regulation of angiogenic regulating factors, of transforming growth factor-β (TGF-β) and of vesicular endothelial growth factor (VEGF) expression in breast cancer cells irradiated with a proton beam was studied. Aromatase activity and mRNA expression, which is correlated with metastasis, were significantly decreased by irradiation with a proton beam in a dose-dependent manner. TGF-β and VEGF transcriptions were also diminished by proton beam irradiation. In contrast, transcription of tissue inhibitors of matrix metalloproteinases (TIMPs), also known as biological inhibitors of matrix metalloproteinases (MMPs), was dose-dependently enhanced. Furthermore, an increase in the expression of TIMPs caused the MMP-9 activity to be diminished and the MMP-9 and the MMP-2 expressions to be decreased. These results suggest that inhibition of angiogenesis by proton beam irradiation in breast cancer cells is closely related to inhibitions of aromatase activity and transcription and to down-regulation of TGF-β and VEGF transcription.

Social factors and aromatase gene expression during adult male-to-female sex change in captive leopard grouper Mycteroperca rosacea.

Science.gov (United States)

Romo-Mendoza, Daniel; Campos-Ramos, Rafael; Vázquez-Islas, Grecia; Burgos-Aceves, Mario A; Esquivel-Gutiérrez, Edgar R; Guerrero-Tortolero, Danitzia A

2018-01-25

Social factors and aromatase gene expression in the leopard grouper Mycteroperca rosacea was studied when captive fish were separated by sex during the reproductive (April-June) and post-reproductive (July-September) seasons. Monosex females, monosex males, and mixed-sex, held in social sextet units were analyzed for sex steroids throughout confinement. At the end of the experiment, the gonad-sex was defined by histology, and gonad and brain aromatase gene expressions were quantified. Only males held in the monosex social units changed sex. Histology showed one male remained unchanged, six were found in a transitional sexual stage, in which two had intersex-predominantly-testes, and four had a more defined intersex ovo-testes pattern, and 11 were immature de novo females (neofemales). Neofemales and most intersex fish did not survive. In spring, 11-ketosterone showed a specific male profile, which suggests that male-to-female sex change was not triggered during the reproductive season. The low steroid levels in summer made it impossible to associate the sex change to a gonad hormonal shift; in September, gonad aromatase gene expression was not significantly different among groups. However, brain aromatase expression in intersex fish was significantly higher than monosex females, mixed-sex females, and neofemale groups. These results suggest that in the absence of female hormonal compounds, and at a time when male gonad steroidogenesis was diminished, the brain mediated male-to-male social-behavioral interactions, including stress, by increasing aromatization, resulting in derived intersex-male, which triggered more aromatization, followed by a sex change. Copyright © 2018 Elsevier Inc. All rights reserved.

Hypothesis testing with computational modeling: linking aromatase inhibition with plasma vitellogenin dynamics in fathead minnows

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Fadrozole inhibits aromatase (CYP19A), a key enzyme that converts testosterone to estradiol (E2). In fish, E2 concentrations control hepatic synthesis ofthe glycolipoprotein vitellogenin (VTG), an egg yolk precursor protein essential to oocyte development and larval survival. Whe...

Immunoexpression of androgen receptors and aromatase in testes of patient with Klinefelter's syndrome.

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Stanisław Fracki

2005-02-01

Full Text Available Klinefelter's syndrome (47, XXY is the most common chromosome aneuploidy in men and is usually characterized by underdeveloped testes and sterility. The aim of the present study was to detect cellular distribution of androgen receptors (AR and aromatase in testes of patient with KS. The tissue sections were processed for morphological and immunohistochemical staining. Additionally, levels of FSH, LH, PRL, estradiol, and testosterone were measured in the plasma. Morphological analysis revealed a complete absence of spermatogenesis. No germ cells were present in seminiferous tubules. In some tubules, nests of apparently degenerating Sertoli cells were found. In the interstitium, Leydig cell hyperplasia was observed. Using immunohistochemistry, nuclear AR staining was detected in Sertoli cells and peritubular cells, whereas in Leydig cells the staining was exclusively cytoplasmic. The immunostaining of aromatase was detected in the cytoplasm of Sertoli cells and Leydig cells. Increased levels of gonadotropins and decreased level of testosterone concomitantly with the cytoplasmic localization of AR in Leydig cells might contribute to the impaired testicular function in patient with KS.

Several synthetic progestins disrupt the glial cell specific-brain aromatase expression in developing zebra fish

International Nuclear Information System (INIS)

Cano-Nicolau, Joel; Garoche, Clémentine; Hinfray, Nathalie; Pellegrini, Elisabeth; Boujrad, Noureddine; Pakdel, Farzad; Kah, Olivier; Brion, François

2016-01-01

The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC 50 ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a radial glial cell context using U251-MG cells co-transfected with zebrafish ER subtypes (zfERα, zfERβ1 or zfERβ2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in radial glial cells. Given the crucial role of radial glial cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation. - Highlights: • P4 + 24 progestins

Several synthetic progestins disrupt the glial cell specific-brain aromatase expression in developing zebra fish

Energy Technology Data Exchange (ETDEWEB)

Cano-Nicolau, Joel [Team NEED, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Garoche, Clémentine; Hinfray, Nathalie [Unité d' Ecotoxicologie in vitro et in vivo , Institut National de l' Environnement Industriel et des Risques (INERIS), BP 2, 60550 Verneuil-en-Halatte (France); Pellegrini, Elisabeth [Team NEED, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Boujrad, Noureddine; Pakdel, Farzad [TREK, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Kah, Olivier, E-mail: oliver.kah@univ-rennes1.fr [Team NEED, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Brion, François, E-mail: francois.brion@ineris.fr [Unité d' Ecotoxicologie in vitro et in vivo , Institut National de l' Environnement Industriel et des Risques (INERIS), BP 2, 60550 Verneuil-en-Halatte (France)

2016-08-15

The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC{sub 50} ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a radial glial cell context using U251-MG cells co-transfected with zebrafish ER subtypes (zfERα, zfERβ1 or zfERβ2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in radial glial cells. Given the crucial role of radial glial cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation. - Highlights: • P4 + 24

Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay

DEFF Research Database (Denmark)

Jacobsen, Naja Wessel; Hansen, Cecilie Hurup; Nellemann, Christine

2015-01-01

shown to inhibit the aromatase enzyme in both types of aromatase assays. The IC50 values ranged from 3 to 600μM. All five SSRIs, were further investigated in the H295R cell line. All compounds altered the steroid secretion from the cells, the lowest observed effect levels were 0.9μM and 3.1μ....... In this study we investigated whether the endocrine effect due to SSRI exposure could be detected in well adopted in vitro steroidogenesis assays, two versions of the aromatase enzyme inhibition assay and the H295R cell assay. The five drugs citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, were......M for sertraline and fluvoxamine, respectively. In general the H295R cell assay was more sensitive to SSRI exposure than the two aromatase assays, up to 20 times more sensitive. This indicates that the H295R cell line is a better tool for screening endocrine disrupting effects. Our findings show that the endocrine...

Estrogens and male reproduction: a new concept

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S. Carreau

2007-06-01

Full Text Available The mammalian testis serves two main functions: production of spermatozoa and synthesis of steroids; among them estrogens are the end products obtained from the irreversible transformation of androgens by a microsomal enzymatic complex named aromatase. The aromatase is encoded by a single gene (cyp19 in humans which contains 18 exons, 9 of them being translated. In rats, the aromatase activity is mainly located in Sertoli cells of immature rats and then in Leydig cells of adult rats. We have demonstrated that germ cells represent an important source of estrogens: the amount of P450arom transcript is 3-fold higher in pachytene spermatocytes compared to gonocytes or round spermatids; conversely, aromatase activity is more intense in haploid cells. Male germ cells of mice, bank voles, bears, and monkeys express aromatase. In humans, we have shown the presence of a biologically active aromatase and of estrogen receptors (alpha and ß in ejaculated spermatozoa and in immature germ cells in addition to Leydig cells. Moreover, we have demonstrated that the amount of P450arom transcripts is 30% lower in immotile than in motile spermatozoa. Alterations of spermatogenesis in terms of number and motility of spermatozoa have been described in men genetically deficient in aromatase. These last observations, together with our data showing a significant decrease of aromatase in immotile spermatozoa, suggest that aromatase could be involved in the acquisition of sperm motility. Thus, taking into account the widespread localization of aromatase and estrogen receptors in testicular cells, it is obvious that, besides gonadotrophins and androgens, estrogens produced locally should be considered to be physiologically relevant hormones involved in the regulation of spermatogenesis and spermiogenesis.

Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries

Energy Technology Data Exchange (ETDEWEB)

Ito, Y.; Fisher, C.R.; Simpson, E.R. (Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)); Conte, F.A.; Grumbach, M.M. (Univ. of California, San Francisco, CA (United States))

1993-11-15

The authors identified two mutations in the CYP19 gene responsible for aromatase deficiency in an 18-year-old 46,XX female with ambiguous external genitalia at birth, primary amenorrhea and sexual infantilism, and polycystic ovaries. The coding exons, namely exons II-X, of the CYP19 gene were amplified by PCR from genomic DNA and sequenced directly. Direct sequencing of the amplified DNA from the patient revealed two single-base changes, at bp 1303 (C[yields]T) and bp 1310 (G[yields]A) in exon X, which were newly found missense mutations and resulted in codon changes of R435C and C437Y, respectively. Subcloning followed by sequencing confirmed that the patient is a compound heterozygote. The results of restriction fragment length polymorphism analysis and direct sequencing of the amplified exon X DNA from the patient's mother indicate maternal inheritance of the R435C mutation. Transient expression experiments showed that the R435C mutant protein had [approx]1.1% of the activity of the wild type, whereas C437Y was totally inactive. Cysteine-437 is the conserved cysteine in the heme-binding region believed to serve as the fifth coordinating ligand of the heme iron. To the authors' knowledge, this patient is the first adult to have described the cardinal features of a syndrome of aromatase deficiency. Recognition that such defects exist will lead to a better understanding of the role of this enzyme in human development and disease.

Nordic Walking as an Exercise Intervention to Reduce Pain in Women With Aromatase Inhibitor-Associated Arthralgia: A Feasibility Study.

Science.gov (United States)

Fields, Jo; Richardson, Alison; Hopkinson, Jane; Fenlon, Deborah

2016-10-01

Women taking aromatase inhibitors as treatment for breast cancer commonly experience joint pain and stiffness (aromatase inhibitor-associated arthralgia [AIAA]), which can cause problems with adherence. There is evidence that exercise might be helpful, and Nordic walking could reduce joint pain compared to normal walking. To determine the feasibility of a trial of Nordic walking as an exercise intervention for women with AIAA. A feasibility study was carried out in a sample of women with AIAA using a randomized control design. Women were randomized to exercise (six-week supervised group Nordic walking training once per week with an increasing independent element, followed by six weeks 4 × 30 minutes/week independent Nordic walking); or enhanced usual care. Data were collected on recruitment, retention, exercise adherence, safety, and acceptability. The Brief Pain Inventory, GP Physical Activity Questionnaire, and biopsychosocial measures were completed at baseline, six and 12 weeks. Forty of 159 eligible women were recruited and attrition was 10%. There was no increased lymphedema and no long-term or serious injury. Adherence was >90% for weekly supervised group Nordic walking, and during independent Nordic walking, >80% women managed one to two Nordic walking sessions per week. From baseline to study end point, overall activity levels increased and pain reduced in both the intervention and control groups. Our findings indicate that women with AIAA are prepared to take up Nordic walking, complete a six-week supervised course and maintain increased activity levels over a 12-week period with no adverse effects. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Quantitative (q)AOP for aromatase inhibition as case study to advance qAOP development practices

Science.gov (United States)

Here we describe how “read across” of a quantitative adverse outcome pathway (qAOP) developed with data for one chemical can be used to screen impacts of other chemicals. We developed a qAOP starting with inhibition of CYP19A (aromatase) in fathead minnows (FHM) as th...

Distribution of aromatase and sex steroid receptors in the baculum during the rat life cycle: effects of estrogen during the early development of the baculum.

Science.gov (United States)

Yonezawa, Tomohiro; Higashi, Mayuko; Yoshioka, Kazuki; Mutoh, Ken-ichiro

2011-07-01

The baculum, also called os penis, plays an important role during copulation. However, the hormonal regulation of its development remains to be elucidated. To determine the direct involvement of sex steroids in the development of the baculum of rats, the distributions of androgen receptors (ARs), aromatase, and estrogen receptor alpha (ESR1) were observed immunohistochemically. On Postnatal Day 1, the rudiment of the baculum expressed ARs, aromatase, and ESR1. In the proximal segment of the baculum of neonatal rats, ARs were expressed in the parosteal layer but not in the periosteum or osteoblasts. Aromatase was expressed from the parosteal layer to the endosteum, particularly in the inner osteogenic layer. ESR1 was also abundantly expressed in almost all cells from the parosteal layer to the endosteum. ARs, aromatase, and ESR1 were all abundantly expressed during the neonatal period in the hyaline cartilage of the proximal segment and in fibrocartilage of the distal segment of the baculum. Expression in all the tissues was attenuated in an age-dependent manner and became quite weak at puberty. To determine the effect of estrogen on the growth of the baculum, the aromatase inhibitor 1,4,6-androstatrien-3,17-dione (ATD) was subcutaneously injected daily into pregnant rats from Days 19 to 23 of gestation and into pups on postnatal Days 1, 3, 5, 7, and 9. On Day 10, the length of the baculum in the ATD-treated rats was significantly shorter than that in the controls, although the body weight did not change. These findings suggest that not only androgen but also locally aromatized estrogen is involved in the early growth and development of the baculum.

Publishing activities improves undergraduate biology education.

Science.gov (United States)

Smith, Michelle K

2018-06-01

To improve undergraduate biology education, there is an urgent need for biology instructors to publish their innovative active-learning instructional materials in peer-reviewed journals. To do this, instructors can measure student knowledge about a variety of biology concepts, iteratively design activities, explore student learning outcomes and publish the results. Creating a set of well-vetted activities, searchable through a journal interface, saves other instructors time and encourages the use of active-learning instructional practices. For authors, these publications offer new opportunities to collaborate and can provide evidence of a commitment to using active-learning instructional techniques in the classroom.

Biological Activities of Hydrazone Derivatives

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S. Güniz Küçükgüzel

2007-08-01

Full Text Available There has been considerable interest in the development of novel compounds with anticonvulsant, antidepressant, analgesic, antiinflammatory, antiplatelet, antimalarial, antimicrobial, antimycobacterial, antitumoral, vasodilator, antiviral and antischistosomiasis activities. Hydrazones possessing an azometine -NHN=CH- proton constitute an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. These observations have been guiding for the development of new hydrazones that possess varied biological activities.

Aromatase inhibitors in stimulated IVF cycles

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Tournaye Herman

2011-06-01

Full Text Available Abstract Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels

Effects of bisphenol A-related diphenylalkanes on vitellogenin production in male carp (Cyprinus carpio) hepatocytes and aromatase (CYP19) activity in human H295r adrenocortical carcinoma cells

International Nuclear Information System (INIS)

Letcher, Robert J.; Sanderson, J. Thomas; Bokkers, Abraham; Giesy, John P.; Berg, Martin van den

2005-01-01

The present study investigated the effects of the known xenoestrogen bisphenol A (BPA) relative to eight BPA-related diphenylalkanes on estrogen receptor (ER)-mediated vitellogenin (vtg) production in hepatocytes from male carp (Cyprinus carpio), and on aromatase (CYP19) activity in the human adrenocortical H295R carcinoma cell line. Of the eight diphenylalkanes, only 4,4'-(hexafluoropropylidene)diphenol (BHF) and 2,2'-bis(4-hydroxy-3-methylphenyl)propane (BPRO) induced vtg, i.e., to a maximum of 3% to 4% (at 100 μM) compared with 8% for BPA relative to the maximum induction by 17β-estradiol (E2, 1 μM). Bisphenol A diglycidyl ether (BADGE) was a potent antagonist of vtg production with an IC50 of 5.5 μM, virtually 100% inhibition of vtg at 20 μM, and an inhibitive (IC50) potency about one-tenth that of the known ER antagonist tamoxifen (IC50, 0.6 μM). 2,2'-Diallyl bisphenol A, 4,4'-(1,4-phenylene-diisopropylidene)bisphenol, BPRO, and BHF were much less inhibitory with IC50 concentrations of 20-70 μM, and relative potencies of 0.03 and 0.009 with tamoxifen. Bisphenol ethoxylate showed no anti-estrogenicity (up to 100 μM), and 4,4'-isopropylidene-diphenol diacetate was only antagonistic at 100 μM. When comparing the (anti)estrogenic potencies of these bisphenol A analogues/diphenylalkanes, anti-estrogenicity occurred at lower concentrations than estrogenicity. 4,4'-Isopropylidenebis(2,6-dimethylphenol) (IC50, 2.0 μM) reduced E2-induced (EC50, 100 nM) vtg production due to concentration-dependent cytotoxicity as indicated by a parallel decrease in MTT activity and vtg, whereas the remaining diphenylalkanes did not cause any cytotoxicity relative to controls. None of the diphenylalkanes (up to 100 μM) induced EROD activity indicating that concentration-dependent, CYP1A enzyme-mediated metabolism of E2, or any Ah-receptor-mediated interaction with the ER, was not a likely explanation for the observed anti-estrogenic effects. At concentrations as great as 100

Perinatal administration of aromatase inhibitors in rodents as animal models of human male homosexuality: similarities and differences.

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Olvera-Hernández, Sandra; Fernández-Guasti, Alonso

2015-01-01

In this chapter we briefly review the evidence supporting the existence of biological influences on sexual orientation. We focus on basic research studies that have affected the estrogen synthesis during the critical periods of brain sexual differentiation in male rat offspring with the use of aromatase inhibitors, such as 1,4,6-androstatriene-3,17 (ATD) and letrozole. The results after prenatal and/or postnatal treatment with ATD reveal that these animals, when adults, show female sexual responses, such as lordosis or proceptive behaviors, but retain their ability to display male sexual activity with a receptive female. Interestingly, the preference and sexual behavior of these rats vary depending upon the circadian rhythm.Recently, we have established that the treatment with low doses of letrozole during the second half of pregnancy produces male rat offspring, that when adults spend more time in the company of a sexually active male than with a receptive female in a preference test. In addition, they display female sexual behavior when forced to interact with a sexually experienced male and some typical male sexual behavior when faced with a sexually receptive female. Interestingly, these males displayed both sexual behavior patterns spontaneously, i.e., in absence of exogenous steroid hormone treatment. Most of these features correspond with those found in human male homosexuals; however, the "bisexual" behavior shown by the letrozole-treated rats may be related to a particular human population. All these data, taken together, permit to propose letrozole prenatal treatment as a suitable animal model to study human male homosexuality and reinforce the hypothesis that human sexual orientation is underlied by changes in the endocrine milieu during early development.

Fish with thermolabile sex determination (TSD) as models to study brain sex differentiation.

Science.gov (United States)

Blázquez, Mercedes; Somoza, Gustavo M

2010-05-01

As fish are ectothermic animals, water temperature can affect their basic biological processes such as larval development, growth and reproduction. Similar to reptiles, the incubation temperature during early phases of development is capable to modify sex ratios in a large number of fish species. This phenomenon, known as thermolabile sex determination (TSD) was first reported in Menidia menidia, a species belonging to the family Atherinopsidae. Since then, an increasing number of fish have also been found to exhibit TSD. Traditionally, likewise in reptiles, several TSD patterns have been described in fish, however it has been recently postulated that only one, females at low temperatures and males at high temperatures, may represent the "real" or "true" TSD. Many studies regarding the influence of temperature on the final sex ratios have been focused on the expression and activity of gonadal aromatase, the enzyme involved in the conversion of androgens into estrogens and encoded by the cyp19a1a gene. In this regard, teleost fish, may be due to a whole genome duplication event, produce another aromatase enzyme, commonly named brain aromatase, encoded by the cyp19a1b gene. Contrary to what has been described in other vertebrates, fish exhibit very high levels of aromatase activity in the brain and therefore they synthesize high amounts of neuroestrogens. However, its biological significance is still not understood. In addition, the mechanism whereby temperature can induce the development of a testis or an ovary still remains elusive. In this context the present review is aimed to discuss several theories about the possible role of brain aromatase using fish as models. The relevance of brain aromatase and therefore of neuroestrogens as the possible cue for gonadal differentiation is raised. In addition, the possible role of brain aromatase as the way to keep the high levels of neurogenesis in fish is also considered. Several key examples of how teleosts and aromatase

Effect of a hormone-releasing intrauterine system (Mirena® on aromatase and Cox-2 expression in patients with adenomyosis submitted or not, to endometrial resection

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Maia R

2012-04-01

Full Text Available Hugo Maia Jr1,2, Clarice Haddad1, Julio Casoy1, Rebeca Maia1, Nathanael Pinheiro3, Elsimar M Coutinho11Centro de Pesquisa e Assistência em Reprodução Humana (CEPARH, 2Itaigara Memorial Day Hospital, 3IMAGEPAT, Salvador, Bahia, BrazilObjective: To investigate the effect of a levonorgestrel-releasing intrauterine system (Mirena® on aromatase and cyclooxygenase-2 (Cox-2 expression in the endometrium of patients with adenomyosis who were submitted to endometrial resection at the time of insertion, compared to a group not submitted to endometrial resection and a group of controls with adenomyosis not submitted to any previous hormonal treatment.Patients and methods: Patients with adenomyosis (n = 89 were included in this study. Twenty-two patients had been using Mirena® for 5 years but had not been submitted to endometrial resection prior to insertion of the device. Twenty-four patients were submitted to endometrial resection at the time of Mirena® insertion. The remaining 43 patients with adenomyosis had undergone no previous hormonal treatment and served as a control group. Cox-2 and aromatase expression were determined in the endometrium by immunohistochemistry.Results: Use of Mirena® for 5 years reduced aromatase expression in the endometrium; however, this reduction was significantly greater in the uteri previously submitted to endometrial resection. The reduction in Cox-2 expression was significant only in the uteri submitted to endometrial resection followed by the insertion of Mirena®.Conclusion: Endometrial resection followed by the insertion of Mirena® was associated with greater rates of amenorrhea in patients with adenomyosis, which in turn were associated with a more effective inhibition of aromatase and Cox-2 expression in the endometrium.Keywords: aromatase, Mirena®, adenomyosis, Cox-2, endometrium, levonorgestrel

Determination and confirmation of selective estrogen receptor modulators (SERMs), anti-estrogens and aromatase inhibitors in bovine and porcine urine using UHPLC-MS/MS.

Science.gov (United States)

Meijer, Thijs; Essers, Martien L; Kaklamanos, George; Sterk, Saskia S; van Ginkel, Leendert A

2017-04-01

Selective estrogen receptor modulators (SERMs), anti-estrogens and aromatase inhibitors are prohibited in human sports doping. However, they also present a risk of being used illegally in animal husbandry for fattening purposes. A method was developed and validated using UHPLC-MS/MS for the determination and confirmation of SERMs, anti-estrogens and aromatase inhibiters in bovine and porcine urine. This method was used in a survey of more than 200 bovine and porcine urine samples from Dutch farms. In 18 out of 103 porcine urine samples (17%) and two out of 114 bovine samples (2%) formestane, an aromatase inhibitor, was detected. None of the other compounds was detected. From human doping control it is known that formestane can, in some cases, be of natural origin. Analyses of reference samples from untreated bovine and porcine animals demonstrated the presence of formestane in bovine animals, but not yet in porcine animals. Future research will focus on whether the detected formestane in porcine and bovine urine is from endogenous or exogenous origin, using GC-c-IRMS.

Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

DEFF Research Database (Denmark)

Kümler, Iben; Knoop, Ann S; Jessing, Christina A R

2016-01-01

. However, overall survival was not significantly increased. CONCLUSION: Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin...

Biological activities of Lavandula angustifolia essential oil

OpenAIRE

Bílková, Zuzana

2013-01-01

Zuzana Bílková, Biological activities of Lavandula angustifolia essential oil, Thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, thesis author: PharmDr. Jan Martin, PhD., Hradec Králové, 2013, 72 pages. The thesis called "Biological activities of Lavandula angustifolia essential oil" is interested in biological activities of Lavandula angustifolia essential oil, specifically antifungal, antioxidant, anti-inflammatory, cytotoxicity, nematicidal and repellency activit...

Study on the effect of aromatase inhibitors and antiestrogens on the sex differentiation of broiler chicks

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E.A Valizadeh

2011-02-01

Full Text Available During the development of chick embryo, the genotype of the zygote determines the nature of the gonads, which thereafter creates the male or female phenotype. Differentiation of gonads during the period called “critical period for sexual differentiation “is accompanied with beginning of secretion of sexual hormones. Every change in the rate of steroidal hormones concentration during this critical period, affects on the structure of gonads. Therefore, injection of aromatase inhibitors (which blocks the synthesis of estrogen from testostron in 5th day of incubation into the eggs, causes the production of males with female genotype. These sex reversal females have bilateral testes with complete spermatogenesis, having normal physical appearance and behavior. In this study, 14-α-hydroxy 3,6,17, androstan-trion inhibitor (1mg/egg was injected into the eggs. Furthermore, the effect of three anti-estrogens (which blocks the estrogen receptor Tamoxifen, and Clomiphen Citrate and GAR79 were studied. Injection of aromatase inhibitors into the eggs during incubation period caused statistically significant (p

Paternal retrieval behavior regulated by brain estrogen synthetase (aromatase in mouse sires that engage in communicative interactions with pairmates

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Shirin eAkther

2015-12-01

Full Text Available Parental behaviors involve complex social recognition and memory processes and interactive behavior with children that can greatly facilitate healthy human family life. Fathers play a substantial role in child care in a small but significant number of mammals, including humans. However, the brain mechanism that controls male parental behavior is much less understood than that controlling female parental behavior. Fathers of non-monogamous laboratory ICR mice are an interesting model for examining the factors that influence paternal responsiveness because sires can exhibit maternal-like parental care (retrieval of pups when separated from their pups along with their pairmates because of olfactory and auditory signals from the dams. Here we tested whether paternal behavior is related to femininity by the aromatization of testosterone. For this purpose, we measured the immunoreactivity of aromatase (cytochrome P450 family 19 (CYP19, which synthesizes estrogen from androgen, in nine brain regions of the sire. We observed higher levels of aromatase expression in these areas of the sire brain when they engaged in communicative interactions with dams in separate cages. The capacity of sires to retrieve pups was increased following a period of five days spent with the pups as a whole family after parturition, whereas the acquisition of this ability was suppressed in sires treated daily with an aromatase inhibitor. These results suggest that brain aromatization regulates the initiation, development, and maintenance of paternal behavior in the ICR mice.

Brassinosteroids: synthesis and biological activities

Czech Academy of Sciences Publication Activity Database

Oklešťková, Jana; Rárová, Lucie; Kvasnica, Miroslav; Strnad, Miroslav

2015-01-01

Roč. 14, č. 6 (2015), s. 1053-1072 ISSN 1568-7767 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Brassinosteroids * Chemical synthesis * Plant biological activity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.686, year: 2015

A review exploring biological activities of hydrazones

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Garima Verma

2014-01-01

Full Text Available The development of novel compounds, hydrazones has shown that they possess a wide variety of biological activities viz. antimicrobial, anticonvulsant, antidepressant, anti-inflammatory, analgesic, antiplatelet, antimalarial, anticancer, antifungal, antitubercular, antiviral, cardio protective etc., Hydrazones/azomethines/imines possess-NHN = CH- and constitute an important class of compounds for new drug development. A number of researchers have synthesized and evaluated the biological activities of hydrazones. This review aims at highlighting the diverse biological activities of hydrazones.

Musculoskeletal Adverse Events Associated with Adjuvant Aromatase Inhibitors

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Qamar J. Khan

2010-01-01

Full Text Available Musculoskeletal symptoms including arthralgia and myalgia occur frequently in aging women, particularly during the transition to menopause, when plasma estrogens precipitously decline. In postmenopausal women (PMW with breast cancer, third-generation aromatase inhibitors (AIs as adjuvant hormonal therapy have proven to be more effective, and to have a more predictable side effect profile, than tamoxifen. However, AIs further reduce plasma estrogens in PMW, exacerbating musculoskeletal symptoms. Clinical trial data have shown significantly higher incidences of arthralgia and myalgia with AIs compared with women on tamoxifen or placebo. Symptoms may be severe enough to significantly affect quality of life; musculoskeletal symptoms are a frequent reason for discontinuing therapy. In many cases, symptoms can be effectively managed with oral analgesics or other strategies. Early recognition and effective management of musculoskeletal symptoms can help maximize treatment compliance, enabling patients to derive optimal benefit from therapy in terms of preventing recurrence.

Short Stature in Chronic Kidney Disease Treated with Growth Hormone and an Aromatase Inhibitor

OpenAIRE

Mendley, Susan R.; Spyropoulos, Fotios; Counts, Debra R.

2015-01-01

We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correc...

Genus Pouteria: chemistry and biological activity

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Cíntia A. M. Silva

Full Text Available The genus Pouteria belongs to the family Sapotaceae and can be widely found around the World. These plants have been used as building material, as food, because the eatable fruits, as well as remedies in folk medicine. Some biological activities have been reported to species of this genus such as antioxidant, anti-inflammatory, antibacterial and antifungal. However, the real potential of this genus as source of new drugs or phytomedicines remains unknown. Therefore, a review of the so far known chemical composition and biological activities of this genus is presented to stimulate new studies about the species already reported moreover that species have no reference about chemistry or biological activities could be found until now.

Cyclobutane-Containing Alkaloids: Origin, Synthesis, and Biological Activities

OpenAIRE

Sergeiko, Anastasia; Poroikov, Vladimir V; Hanuš, Lumir O; Dembitsky, Valery M

2008-01-01

Present review describes research on novel natural cyclobutane-containing alkaloids isolated from terrestrial and marine species. More than 60 biological active compounds have been confirmed to have antimicrobial, antibacterial, antitumor, and other activities. The structures, synthesis, origins, and biological activities of a selection of cyclobutane-containing alkaloids are reviewed. With the computer program PASS some additional biological activities are also predicted, which point toward ...

High progesterone levels during the luteal phase related to the use of an aromatase inhibitor in breast cancer patients

DEFF Research Database (Denmark)

Alviggi, C; Marci, R; Vallone, R

2017-01-01

OBJECTIVE: To evaluate the hormonal profile in three breast cancer patients who underwent controlled ovarian stimulation in the presence of the aromatase inhibitor letrozole. PATIENTS AND METHODS: In IVF University referral center, a case series of three breast cancer patients who underwent contr...

Effects of the aromatase inhibitor Letrozole on serum immunoglobulin and lysozyme levels in immunized rainbow trout (Oncorhynchus mykiss Walbaum females

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Paria Akbary

2013-12-01

Full Text Available Letrozole is a synthetic aromatase inhibitor and interfere in the committed step in the synthesis of endogenous estrogens from androgens. Also estrogens regulate the immune system in teleost. Changes of 17- β- esrtradiol (E2, serum immunoglobulin and lysozyme levels were measured using a method based on the ability of lysozyme to lyse the bacterium Micrococcus lysodeikticus, enzyme-linked immunosorbent assay (ELISA and ELISA respectively. Twelve broodstocks were injected weekly with 2.5 mg kg-1 letrozole (an endocrine disrupter component two months before spawning season and vaccinated intraperitoneally (i.p with a bacterin (inactivated L. garviae one month before spawning. Twelve broodstocks for vaccination and twelve female rainbow trout as control group were also immiunised (i.p with the bacterin and injected (i.p with PBS, respectively. In the group received 2.5 mg AI kg-1 per week, serum E2 levels were significantly lower than that of other groups. Total immunoglobulin level and lysozyme activity were significantly higher in the parents received 2.5 mg kg-1 per week and were immunized with 10-9 cells ml-1 Lactococcus garvieae  compared to the group which immunized with L. garvieae and the control (non- immunized. The present study, suggests that aromatase inhibitors such as letrozole may be a potential tool to regulate the synthesis of E2, is involved in the hormone- immune system interaction in rainbow trout.

Brain Aromatase Modulates Serotonergic Neuron by Regulating Serotonin Levels in Zebrafish Embryos and Larvae

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Zulvikar Syambani Ulhaq

2018-05-01

Full Text Available Teleost fish are known to express two isoforms of P450 aromatase, a key enzyme for estrogen synthesis. One of the isoforms, brain aromatase (AroB, cyp19a1b, is highly expressed during early development of zebrafish, thereby suggesting its role in brain development. On the other hand, early development of serotonergic neuron, one of the major monoamine neurons, is considered to play an important role in neurogenesis. Therefore, in this study, we investigated the role of AroB in development of serotonergic neuron by testing the effects of (1 estradiol (E2 exposure and (2 morpholino (MO-mediated AroB knockdown. When embryos were exposed to E2, the effects were biphasic. The low dose of E2 (0.005 µM significantly increased serotonin (5-HT positive area at 48 hour post-fertilization (hpf detected by immunohistochemistry and relative mRNA levels of tryptophan hydroxylase isoforms (tph1a, tph1b, and tph2 at 96 hpf measured by semi-quantitative PCR. To test the effects on serotonin transmission, heart rate and thigmotaxis, an indicator of anxiety, were analyzed. The low dose also significantly increased heart rate at 48 hpf and decreased thigmotaxis. The high dose of E2 (1 µM exhibited opposite effects in all parameters. The effects of both low and high doses were reversed by addition of estrogen receptor (ER blocker, ICI 182,780, thereby suggesting that the effects were mediated through ER. When AroB MO was injected to fertilized eggs, 5-HT-positive area was significantly decreased, while the significant decrease in relative tph mRNA levels was found only with tph2 but not with two other isoforms. AroB MO also decreased heart rate and increased thigmotaxis. All the effects were rescued by co-injection with AroB mRNA and by exposure to E2. Taken together, this study demonstrates the role of brain aromatase in development of serotonergic neuron in zebrafish embryos and larvae, implying that brain-formed estrogen is an important factor to

Imidazole: Having Versatile Biological Activities

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Amita Verma

2013-01-01

Full Text Available Imidazoles have occupied a unique position in heterocyclic chemistry, and its derivatives have attracted considerable interests in recent years for their versatile properties in chemistry and pharmacology. Imidazole is nitrogen-containing heterocyclic ring which possesses biological and pharmaceutical importance. Thus, imidazole compounds have been an interesting source for researchers for more than a century. The imidazole ring is a constituent of several important natural products, including purine, histamine, histidine, and nucleic acid. Being a polar and ionisable aromatic compound, it improves pharmacokinetic characteristics of lead molecules and thus is used as a remedy to optimize solubility and bioavailability parameters of proposed poorly soluble lead molecules. There are several methods used for the synthesis of imidazole-containing compounds, and also their various structure reactions offer enormous scope in the field of medicinal chemistry. The imidazole derivatives possess extensive spectrum of biological activities such as antibacterial, anticancer, antitubercular, antifungal, analgesic, and anti-HIV activities. This paper aims to review the biological activities of imidazole during the past years.

Activity of megestrol acetate in postmenopausal women with advanced breast cancer after nonsteroidal aromatase inhibitor failure: a phase II trial.

Science.gov (United States)

Bines, J; Dienstmann, R; Obadia, R M; Branco, L G P; Quintella, D C; Castro, T M; Camacho, P G; Soares, F A; Costa, M E F

2014-04-01

As novel treatments carry substantial price tags and are mostly cost-prohibitive in low- and middle-income countries, there is an urgent need to develop alternatives, such as off-patent drugs. Megestrol acetate (MA) has a longstanding history in the treatment of breast cancer, but recently it is being used less often due to the advent of newer agents. This two-stage phase II trial evaluated the antitumor activity and toxicity of MA in postmenopausal women with hormone-sensitive advanced breast cancer who had experienced disease progression on a third-generation nonsteroidal aromatase inhibitor (NSAI). Eligible patients had metastatic breast cancer treated with a NSAI with at least 6-month progression-free survival (PFS), or relapse after ≥1 year on adjuvant NSAI. Patients received MA at a single daily oral dose of 160 mg. Primary end point was clinical benefit rate (CBR). Forty-eight patients were enrolled. The CBR was 40% [95% confidence interval (CI) 25% to 55%], and the median duration of clinical benefit was 10.0 (95% CI 8.0-14.2) months. The median PFS was 3.9 (95% CI 3.0-4.8) months. The most common grade 3 adverse events were anemia (2%), dyspnea (2%), fatigue (2%), musculoskeletal pain (4%), deep vein thrombosis (10%), and weight gain (2%). This is the first study to prospectively evaluate the efficacy and safety of MA in postmenopausal women with hormone-sensitive disease progressing on a NSAI. MA has demonstrated activity and acceptable tolerability in this setting, and therefore remains a reasonable treatment option in a cost-sensitive environment. These results also provide the background for further evaluation of progestins in the treatment of breast cancer. local trial number, related to the approval by the IRB: CEP 108/06.

Biological responses of progestogen metabolites in normal and cancerous human breast.

Science.gov (United States)

Pasqualini, Jorge R; Chetrite, Gérard S

2010-12-01

At present, more than 200 progestogen molecules are available, but their biological response is a function of various factors: affinity to progesterone or other receptors, their structure, the target tissues considered, biological response, experimental conditions, dose, method of administration and metabolic transformations. Metabolic transformation is of huge importance because in various biological processes the metabolic product(s) not only control the activity of the maternal hormone but also have an important activity of its own. In this regard, it was observed that the 20-dihydro derivative of the progestogen dydrogesterone (Duphaston®) is significantly more active than the parent compound in inhibiting sulfatase and 17β-hydroxysteroid dehydrogenase in human breast cancer cells. Estrone sulfatase activity is also inhibited by norelgestromin, a norgestimate metabolite. Interesting information was obtained with a similar progestogen, tibolone, which is rapidly metabolized into the active 3α/3β-hydroxy and 4-ene metabolites. All these metabolites can inhibit sulfatase and 17β-hydroxysteroid dehydrogenase and stimulate sulfotransferase in human breast cancer cells. Another attractive aspect is the metabolic transformation of progesterone itself in human breast tissues. In the normal breast progesterone is mainly converted to 4-ene derivatives, whereas in the tumor tissue it is converted mostly to 5α-pregnane derivatives. 20α-Dihydroprogesterone is found mainly in normal breast tissue and possesses antiproliferative properties as well as the ability to act as an anti-aromatase agent. Consequently, this progesterone metabolite could be involved in the control of estradiol production in the normal breast and therefore implicated in one of the multifactorial mechanisms of the breast carcinogenesis process. In conclusion, a better understanding of both natural and synthetic hormone metabolic transformations and their control could potentially provide

From molecule to behavior: Brain aromatase (cyp19a1b) characterization, expression analysis and its relation with social status and male agonistic behavior in a Neotropical cichlid fish.

Science.gov (United States)

Ramallo, Martín R; Morandini, Leonel; Birba, Agustina; Somoza, Gustavo M; Pandolfi, Matías

2017-03-01

The enzyme aromatase, responsible for the conversion of C19 androgens to C18 estrogens, exists as two paralogue copies in teleost fish: Cyp19a1a mostly expressed in the gonads, referred as gonadal aromatase, and Cyp19a1b, mostly expressed in the brain, accordingly known as brain aromatase. The neural localization of Cyp19a1b is greatly contained within the social behavior network and mesolimbic reward system in fish, suggesting a strong role of estrogen synthesis in the regulation of social behavior. In this work we aimed to analyze the variation in cyp19a1b expression in brain and pituitary of males of a highly social cichlid, Cichlasoma dimerus (locally known as chanchita), and its relation with inter-individual variability in agonistic behavior in a communal social environment. We first characterized chanchita's cyp19a1b mRNA and deduced amino acid sequence, which showed a high degree of conservation when compared to other teleost brain aromatase sequences, and its tissue expression patterns. Within the brain, Cyp19a1b was solely detected at putative radial glial cells of the forebrain, close to the brain ventricles. We then studied the relative expression levels of cyp19a1b by Real Time PCR in the brain and pituitary of males of different social status, territorial vs. non-territorial, and its relationship with an index of agonistic behavior. We found that even though, brain aromatase expression did not differ between types of males, pituitary cyp19a1b expression levels positively correlated with the index of agonistic behavior. This suggests a novel role of the pituitary in the regulation of social behavior by local estrogen synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

[Cycloferon biological activity characteristics].

Science.gov (United States)

Utkina, T M; Potekhina, L P; Kartashova, O L; Vasilchenko, A S

2014-01-01

Study the effect of cycloferon in experimental and clinical conditions on persistence properties of aurococci as well as features of their morpho-functional reaction by atomic force microscopy. The study was carried out in 12 Staphylococcus aureus clones isolated from mucous membrane of nose anterior part of a resident carrier. The effect of cycloferon in vivo was evaluated in 26 resident staphylococci carriers under the control of anti-carnosine activity of staphylococci. Anti-carnosine activity was determined by O.V. Bukharin et al. (1999), biofilm formation -by G.A. O'Toole et al. (2000). Staphylococci treated with cycloferon were studied by atomic force microscopy in contact mode using scanning probe SMM-2000 microscope. The decrease of persistence properties of staphylococci under the effect of cycloferon in vitro and in vivo may be examined as one of the mechanisms of biological activity of the preparation. A significant increase of S. aureus surface roughness and changes in their morphology under the effect of cycloferon allow stating the disorder of barrier functions in the aurococci cell wall. The data obtained expand the understanding of cycloferon biological activity mechanisms.

Early life exposure to environmental levels of the aromatase inhibitor tributyltin causes masculinisation and irreversible sperm damage in zebrafish (Danio rerio).

Science.gov (United States)

McAllister, Brian G; Kime, David E

2003-11-19

To determine whether early life exposure to tributyltin (TBT), an aromatase inhibitor, impaired reproductive function in fish, Danio rerio were exposed to environmentally realistic levels (0.01-100 ng l(-1)) of TBT from 0 to 30, 30 to 60, and 0 to 70 days post-hatch, and the sex ratio and sperm motility of the adults examined 3-5 months after cessation of exposure. Fish exposed for 70 days to 0.1 ng l(-1) of TBT, a concentration presently below the detection limit in water, showed a male biased population which produced a high incidence of sperm lacking flagella. At 1 ng l(-1), the motility of sperm was significantly lower than that of control fish, while at 10 ng l(-1), all sperm lacked flagella and, at 100 ng l(-1), milt volume had increased. The effect of exposure on sex ratio was similar after exposure from 0 to 70 and 0 to 30 days, but even 100 ng l(-1) gave only 65% males after exposure from 30 to 60 days. Effects on sperm motility and morphology and on milt volume were less pronounced after 30 day than 70 day exposure. Our data suggest that screening for aromatase inhibiting activity and assessment of its risks in early life to human and wildlife fertility needs to be urgently addressed, and that the reproductive toxicity of TBT may presently be underestimated.

New insights about the evaluation of human sperm quality: the aromatase example.

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A Saad

2010-01-01

Full Text Available Male contribution to the couple's infertility is at first evaluated by the routine examination of semen parameters upon optical microscopy providing valuable information for a rational initial diagnosis and for a clinical management of infertility. But the different forms of infertility defined according to the WHO criteria especially teratozoospermia are not always related to the chromatin structure or to the fertilization capacity. New investigations at the molecular level (transcript and protein could be developed in order to understand the nature of sperm malformation responsible of human infertility and thus to evaluate the sperm quality. The profile analysis of spermatozoal transcripts could be considered as a fingerprint of the past spermatogenic events. The selection of representative transcripts of normal spermatozoa remains complex because a differential expression (increased, decreased or not modified levels of specific transcripts has been revealed between immotile and motile sperm fractions issued from normozoospermic donors. Microarrays tests or real-time quantitative PCR could be helpful for the identification of factors involved in the male infertility. Differences in the expression of specific transcripts have been reported between normal and abnormal semen samples. With the aromatase example, we have noted a negative strong correlation between the amount of transcript and the percentage of abnormal forms especially in presence of head defects. Immunocytochemical procedures using fluorescent probes associated with either confocal microscopy or flow cytometry can be also helpful to proceed with further investigations about the localization of proteins in the compartmentalized spermatozoa or the acrosome reaction. The dual location of aromatase both in the equatorial segment, the mid-piece and the tail could explain the double role of this enzyme in acrosome reaction and motility.

Breast Cancer, Aromatase Inhibitor Therapy, and Sexual Functioning: A Pilot Study of the Effects of Vaginal Testosterone Therapy

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Melissa Dahir, DNP, IF

2014-04-01

Conclusions: The use of a compounded testosterone vaginal cream applied daily for 4 weeks improves reported sexual health quality of life in women with breast cancer taking AIs. Dahir M and Travers‐Gustafson D. Breast cancer, aromatase inhibitor therapy, and sexual functioning: A pilot study of the effects of vaginal testosterone therapy. Sex Med 2014;2:8–15.

GP88 (PC-Cell Derived Growth Factor, progranulin stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

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Sabnis Gauri

2011-06-01

Full Text Available Abstract Background Aromatase inhibitors (AI that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+ breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88, also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells Methods We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined. Results GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole. Conclusion Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.

Aromatase inhibitors - a viable option for recurrent granulosa cell tumour of ovary: overview and case report

International Nuclear Information System (INIS)

Munem, A.A.; Bahrani, B.A.; Mehdi, I.

2012-01-01

Granulosa cell tumour of the ovary in adults is a rare tumour of low malignant potential affecting middle aged peri or post menopausal patients. These tumours are often diagnosed at an early stage, due to their hormonally active nature. They, however, have unique distinguishing histologic features and behaviour of frequent and late local or systemic relapses. The diagnosis can be challenging with unusual presentations. There is high association of endometrial carcinoma. Surgery is the mainstay of management in early low risk disease, while radiotherapy and systemic platinum based chemotherapy are employed in higher stage with poor prognostic indices. Survival is good in early stage disease. Recurrent, progressive, and treatment refractory disease is not infrequent and poses management challenge. Endocrine manipulation and hormone treatment are employed in few cases with equivocal results, as reported in literature. We present a case of recurrent and treatment refractory GCT in a postmenopausal patient, managed by aromatase inhibitor Anastrozole with reasonable efficacy. (author)

In vivo imaging of brain aromatase in female baboons: [11C]vorozole kinetics and effect of the menstrual cycle.

Science.gov (United States)

Pareto, Deborah; Biegon, Anat; Alexoff, David; Carter, Pauline; Shea, Coreen; Muench, Lisa; Xu, Youwen; Fowler, Joanna S; Kim, Sunny W; Logan, Jean

2013-01-01

The aim of this work was to quantify the brain distribution of the enzyme aromatase in the female baboon with positron emission tomography and the tracer [11C]vorozole using three different quantification methods for estimating the total distribution volume (V(T)): a graphical method, compartment modeling, and a tissue to plasma ratio. The graphical model and the compartment modeling gave similar estimates to the data and similar values (correlation R  =  .988; p  =  .0001). [11C]Vorozole shows a rapid uptake by the brain followed by a relatively constant accumulation, suggesting the possibility of using the tissue to plasma ratio as an estimate of V(T). The highest uptake of [11C]vorozole in the baboon brain was measured in the amygdala, followed by the preoptic area and hypothalamus, basal ganglia, and cortical areas. Pretreatment studies with vorozole or letrozole showed a generalized decrease in brain accumulation and V(T). The results suggested that the physiologic changes in gonadal hormone levels accompanying the menstrual cycle had a significant effect on brain aromatase V(T).

The Biological Activities of Sesterterpenoid-Type Ophiobolins

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Wei Tian

2017-07-01

Full Text Available Ophiobolins (Ophs are a group of tricarbocyclic sesterterpenoids whose structures contain a tricyclic 5-8-5 carbotricyclic skeleton. Thus far, 49 natural Ophs have been reported and assigned into A–W subgroups in order of discovery. While these sesterterpenoids were first characterized as highly effective phytotoxins, later investigations demonstrated that they display a broad spectrum of biological and pharmacological characteristics such as phytotoxic, antimicrobial, nematocidal, cytotoxic, anti-influenza and inflammation-promoting activities. These bioactive molecules are promising drug candidates due to the developments of their anti-proliferative activities against a vast number of cancer cell lines, multidrug resistance (MDR cells and cancer stem cells (CSCs. Despite numerous studies on the biological functions of Ophs, their pharmacological mechanism still requires further research. This review summarizes the chemical structures, sources, and biological activities of the oph family and discusses its mechanisms and structure–activity relationship to lay the foundation for the future developments and applications of these promising molecules.

The Biological Activities of Sesterterpenoid-Type Ophiobolins.

Science.gov (United States)

Tian, Wei; Deng, Zixin; Hong, Kui

2017-07-18

Ophiobolins (Ophs) are a group of tricarbocyclic sesterterpenoids whose structures contain a tricyclic 5-8-5 carbotricyclic skeleton. Thus far, 49 natural Ophs have been reported and assigned into A-W subgroups in order of discovery. While these sesterterpenoids were first characterized as highly effective phytotoxins, later investigations demonstrated that they display a broad spectrum of biological and pharmacological characteristics such as phytotoxic, antimicrobial, nematocidal, cytotoxic, anti-influenza and inflammation-promoting activities. These bioactive molecules are promising drug candidates due to the developments of their anti-proliferative activities against a vast number of cancer cell lines, multidrug resistance (MDR) cells and cancer stem cells (CSCs). Despite numerous studies on the biological functions of Ophs, their pharmacological mechanism still requires further research. This review summarizes the chemical structures, sources, and biological activities of the oph family and discusses its mechanisms and structure-activity relationship to lay the foundation for the future developments and applications of these promising molecules.

STRUCTURES AND BIOLOGICAL ACTIVITY OF CUPROPHYLLINS

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Martynov A.V.

2017-06-01

Full Text Available Chlorophylls (a, b are the porphyrin compounds and most common chemical in the plant’s world. In fact, these compounds are an obligatory intermediate product both in energy metabolism and in plant catabolism. At the same time, currently there are few pharmaceutical preparations on the pharmaceutical market based on chlorophylls. Dyes based on hydrolyzed chlorophyll are successfully used in the food industry. Commercial chlorophylline is a copper complex of hydrolyzed chlorophylls. As shown earlier in TLC, the chlorophyllin mixture contains a large number of different compounds. It is like water-soluble saponified derivatives in the form of sodium-magnesium complexes, and similar structures in the form of a complex with copper. The latter are more brightly colored, soluble in water and widely used as coloring agents in cooking. In this case, if the initial chlorophyll was not found to have a pronounced biological activity, the substituted derivatives in the form of copper complexes possessed a number of new unique biological properties. Non-hydrolyzed hydrophobic cuprophylline obtained from eucalyptus leaves possessed high antimicrobial activity to most strains of staphylococci, inclusion resistant to antimicrobials and multiresistant strains. This drug is called Chlorophyllipt, it is allowed to be used as a medicinal product and is one of the oldest antibacterial drugs from plants on the market. It is marketed as ethanoic and oily solutions for topical use, and as an alcohol solution for intravenous injections. Its main purpose is the fight against staphylococcal infections. Recently, found that the oral administration of chlorophyllipt activates cellular immunity and indirectly exhibits antiviral activity. Another compound of cuprophyllin is water-soluble chlorophyllin. Some authors show the variability of the structure and biological activity of cuprophyllins. Different derivatives of chlorophyll have different biological activity

Acupuncture does not ameliorate metabolic disturbances in the P450 aromatase inhibitor-induced rat model of polycystic ovary syndrome.

Science.gov (United States)

Maliqueo, Manuel; Benrick, Anna; Marcondes, Rodrigo Rodrigues; Johansson, Julia; Sun, Miao; Stener-Victorin, Elisabet

2017-01-01

What is the central question of this study? The effectiveness of low-frequency electroacupuncture in the treatment of metabolic disorders associated with polycystic ovary syndrome (PCOS), an endocrine-metabolic disorder characterized by an imbalance in sex steroid production, is controversial. What is the main finding and its importance? In a rat model of PCOS induced by the inhibition of P450 aromatase, low-frequency electroacupuncture increased low-density lipoprotein-cholesterol but did not improve the insulin resistance or the adipose tissue dysfunction, suggesting that a balance of sex steroids is needed to restore the metabolic function in this rat model of PCOS. Low-frequency electroacupuncture restores sex steroid synthesis and sympathetic activity in women with polycystic ovary syndrome, which may ameliorate its metabolic disturbances, probably by modulating sympathetic nerve activity or sex steroid synthesis. We investigated whether low-frequency electroacupuncture regulates the metabolic function to the same extent as treatment with estradiol or β-adrenergic blocking in a rat model of polycystic ovary syndrome induced by a P450 aromatase inhibitor (letrozole). Letrozole (200 μg day -1 ) or placebo pellets were implanted in prepubertal Wistar rats. Six weeks thereafter, rats were treated for 5-6 weeks with the following: low-frequency electroacupuncture (5 days per week); a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg kg -1 , 5 days per week); or 17β-estradiol (2.0 μg) every fourth day. Body weight development, body composition, locomotor activity, insulin sensitivity, tissue-specific glucose uptake, lipid profile, adipocyte size, serum concentrations of adiponectin and insulin, and gene expression in inguinal fat were measured. All treatments increased circulating levels of low-density lipoprotein-cholesterol. Estradiol treatment restored locomotor activity and increased insulin sensitivity but did not modify the glucose uptake in

Leptin, its receptor and aromatase expression in deep infiltrating endometriosis.

Science.gov (United States)

Gonçalves, Helder F; Zendron, Carolina; Cavalcante, Fernanda S; Aiceles, Verônica; Oliveira, Marco Aurélio P; Manaia, Jorge Henrique M; Babinski, Márcio A; Ramos, Cristiane F

2015-08-05

The aim of this study was to evaluate the leptin levels in the serum and peritoneal fluid (PF) and the protein expression in three different peritoneal ectopic implants in patients who underwent surgery for deep infiltrating endometriosis. All patients had been treated at the Department of Gynecology of the Pedro Ernesto University Hospital, Rio de Janeiro. The study group consisted of 15 patients who underwent surgery for adnexal masses and infertility, while the control group consisted of ten women who underwent surgery for tubal ligation. Peritoneal fluid and samples tissues were collected during surgery. Serum samples were obtained before anesthesia. In this study, the leptin levels in the serum and peritoneal fluid (PF) were evaluated by ELISA. The protein expression of leptin and its receptors (ObR) and aromatase enzyme were evaluated by Western blot analysis of the intestine, uterosacral ligament and vaginal septum in the ectopic implants. The t-test and one-way ANOVA with Holm-Sìdak post-test were used, and p endometriosis = 19.2 ng/mL ± 1.84, p endometriosis = 7.71 ng/mL ± 0.59, p = 0.18). Comparing women with and without ovarian implants, the leptin levels in both the serum and PF were significantly higher in women without ovarian implants (serum: with ovarian implant = 15.85 ± 1.99; without ovarian implant = 23.14 ± 2.60; ng/mL, p = 0.04; PF: with ovarian implant = 4.28 ± 1.30; without ovarian implant = 11.18 ± 2.98;ng/mL, p = 0.048). The leptin, ObR and aromatase protein expression levels were increased in lesions in the vaginal septum and were decreased in the intestine lesions. This study reports several interesting associations between the leptin levels in serum, peritoneal fluid, and tissue samples and the localization of the ectopic endometrium. Although this study does not provide a clear picture of the role of leptin in the development and progression of peritoneal implants

Short Stature in Chronic Kidney Disease Treated with Growth Hormone and an Aromatase Inhibitor

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Susan R. Mendley

2015-01-01

Full Text Available We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correction of height deficit. This strategy may be appropriate for children with chronic kidney disease and short stature who are in puberty.

Multifunctional and biologically active matrices from multicomponent polymeric solutions

Science.gov (United States)

Kiick, Kristi L. (Inventor); Yamaguchi, Nori (Inventor)

2010-01-01

The present invention relates to a biologically active functionalized electrospun matrix to permit immobilization and long-term delivery of biologically active agents. In particular the invention relates to a functionalized polymer matrix comprising a matrix polymer, a compatibilizing polymer and a biomolecule or other small functioning molecule. In certain aspects the electrospun polymer fibers comprise at least one biologically active molecule functionalized with low molecular weight heparin. Examples of active molecules that may be used with the multicomponent polymer of the invention include, for example, a drug, a biopolymer, for example a growth factor, a protein, a peptide, a nucleotide, a polysaccharide, a biological macromolecule or the like. The invention is further directed to the formation of functionalized crosslinked matrices, such as hydrogels, that include at least one functionalized compatibilizing polymer capable of assembly.

Protocol for Exercise Program in Cancer and Cognition (EPICC): A randomized controlled trial of the effects of aerobic exercise on cognitive function in postmenopausal women with breast cancer receiving aromatase inhibitor therapy.

Science.gov (United States)

Gentry, Amanda L; Erickson, Kirk I; Sereika, Susan M; Casillo, Frances E; Crisafio, Mary E; Donahue, Patrick T; Grove, George A; Marsland, Anna L; Watt, Jennifer C; Bender, Catherine M

2018-04-01

The Exercise Program in Cancer and Cognition (EPICC) Study is a randomized controlled trial designed to test the effects of moderate-intensity aerobic exercise on cognitive function in postmenopausal women with early-stage breast cancer during the first six months of aromatase inhibitor therapy. It is estimated that up to 75% of survivors of breast cancer experience cognitive impairment related to disease and treatment. At present, there are no known interventions to improve or manage cognitive function for women with breast cancer. Here, we describe a single-blinded, randomized controlled trial with allocation of 254 postmenopausal women with early-stage breast cancer to a supervised six-month aerobic exercise intervention or usual care. Prior to beginning aromatase inhibitor (AI) therapy, participants complete baseline assessments of cognitive function, cardiorespiratory fitness, blood-based biomarkers, physical activity and sleep, and symptoms (fatigue, sleep problems, depressive symptoms, anxiety). A random subset of participants (n = 150) undergoes neuroimaging procedures that include structural and functional magnetic resonance imaging assessments. All participants maintain an activity diary; physical activity and sleep monitoring is repeated three and seven months post-randomization. The remaining baseline assessments are repeated seven months post-randomization. If successful, exercise could be a low-cost method to improve cognitive function in women with breast cancer that is easily adaptable to the home or community. Clinicaltrials.govNCT02793921. Registered 20 May 2016. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of Muramyl Dipeptide in Lipopolysaccharide-Mediated Biological Activity and Osteoclast Activity

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Hideki Kitaura

2018-01-01

Full Text Available Lipopolysaccharide (LPS is an endotoxin and bacterial cell wall component that is capable of inducing inflammation and immunological activity. Muramyl dipeptide (MDP, the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is another inflammation-inducing molecule that is ubiquitously expressed by bacteria. Several studies have shown that inflammation-related biological activities were synergistically induced by interactions between LPS and MDP. MDP synergistically enhances production of proinflammatory cytokines that are induced by LPS exposure. Injection of MDP induces lethal shock in mice challenged with LPS. LPS also induces osteoclast formation and pathological bone resorption; MDP enhances LPS induction of both processes. Furthermore, MDP enhances the LPS-induced receptor activator of NF-κB ligand (RANKL expression and toll-like receptor 4 (TLR4 expression both in vivo and in vitro. Additionally, MDP enhances LPS-induced mitogen-activated protein kinase (MAPK signaling in stromal cells. Taken together, these findings suggest that MDP plays an important role in LPS-induced biological activities. This review discusses the role of MDP in LPS-mediated biological activities, primarily in relation to osteoclastogenesis.

Short-term androgen priming by use of aromatase inhibitor and hCG before controlled ovarian stimulation for IVF. A randomized controlled trial

DEFF Research Database (Denmark)

Lossl, K; Andersen, C Yding; Loft, A

2008-01-01

Temporary exposure of follicles to increased levels of androgens may augment follicular responsiveness. The present study tested whether short-term androgen priming by aromatase inhibitor and human chorionic gonadotrophin (hCG) before controlled ovarian stimulation (COS) increases the number of top......-quality embryos after IVF/ICSI....

A game of two? Gene expression analysis of brain (cyp19a1b) and gonadal (cyp19a1a) aromatase in females of a Neotropical cichlid fish through the parental care period and removal of the offspring.

Science.gov (United States)

Ramallo, Martín R; Honji, Renato M; Birba, Agustina; Morandini, Leonel; Varela, María L; Genovese, Griselda; Moreira, Renata G; Somoza, Gustavo M; Pandolfi, Matías

2017-10-01

For many species parental behavior is essential for the survival of the offspring. While the ultimate causes of teleost parental behavior have been widely studied, comparatively little is known about its proximate causes. The aim of this study was to analyze the yet unexplored, potential dual role of brain and gonadal aromatases, the enzymes responsible for the conversion of androgens to estrogens in the brains and gonads of teleosts, respectively, on the different stages of the maternal care period of the biparental cichlid Cichlasoma dimerus, locally known as chanchita. By immunohistochemistry we analyzed the neural distribution of brain aromatase and observed it exclusively within the forebrain, including areas involved in the regulation of parental behavior. We next analyzed the gene expression of brain aromatase in the brain, and gonadal aromatase in the ovary, of female chanchitas through the parental care period. To further characterize the physiological environment associated to maternal care, we also evaluated sex steroid levels (17β-estradiol, testosterone and 11-ketotestoterone) and ovarian follicle percentage. The onset of parental behavior specifically downregulated sex steroids synthesis and the rate of ovarian maturation, as denoted by a more than 10-fold decrease in steroid levels and delayed detection of mature follicles in females with offspring, compared to females which eggs were removed. Gene expression levels of both aromatases were independent of maternal care at the evaluated time points, even though they varied during the parental care period. Copyright © 2017 Elsevier Inc. All rights reserved.

Ethnobotanical and biological activities of Leptadenia pyrotechnica ...

African Journals Online (AJOL)

Conclusion: This review includes the substance of different ethnobotanical uses, phytochemistry and exclusive capability of this plant in the field of anti-microbial and human disease activities. Key words: Leptadenia pyrotechnica, Biological activities, Desert plant, Ethnobotanical, Phytochemical activity, phytochemistry.

Bone Scan in Detection of Biological Activity in Nonhypertrophic Fracture Nonunion

OpenAIRE

Gandhi, Sunny J.; Rabadiya, Bhavdeep

2017-01-01

Biological activity of the fracture site is very important factor in treatment planning of fracture nonunion. If no biological activity is detected, then an autologous bone graft can be supplemented or osteogenic supplementations, such as bone morphogenetic protein is given. If biological activity is present, then secure fixation is sufficient to achieve bony union. Biological activity of nonunions is usually assessed by conventional radiographs. The presence of callus formation is usually as...

Endocrine disrupting chemicals (bisphenol A, 4-nonylphenol, 4-tert-octylphenol) modulate expression of two distinct cytochrome P450 aromatase genes differently in gender types of the hermaphroditic fish Rivulus marmoratus.

Science.gov (United States)

Lee, Young-Mi; Seo, Jung Soo; Kim, Il-Chan; Yoon, Yong-Dal; Lee, Jae-Seong

2006-06-30

To understand the effect of endocrine-disrupting chemicals (EDCs) on cytochrome P450 aromatase (rm-cyp19) gene expression between gender types in the hermaphroditic fish Rivulus marmoratus, we cloned two distinct rm-cyp19 genes using RT-PCR with degenerative primers, obtained full-length cDNAs using 5'- and 3'-RACE-PCR methods, and completely sequenced them. The brain aromatase (rm-cyp19b) cDNA consisted of 2,124 bp including the open reading frame (ORF), which encoded a putative protein of 505 amino acids. The ovarian aromatase (rm-cyp19a) cDNA consisted of 2,075 bp, including the ORF encoding a putative protein of 516 amino acids. Expression patterns of rm-cyp19b and rm-cyp19a mRNAs were investigated in embryos of different developmental stages and in seven different tissues of adult fish. The rm-cyp19b gene in hermaphrodite and secondary male R. marmoratus was predominantly expressed in the brain, while the rm-cyp19a gene was expressed gender-specifically in the gonad. The expression of rm-cyp19b mRNA increased from stage 1 (2 d post fertilization) to stage 4 (12 d post fertilization) in a developmental stage-dependent manner but steeply decreased in the hatching stage. Compared to the rm-cyp19b gene, the abundance of ovarian aromatase rm-cyp19a transcripts was very low, and its expression was first detected at stage 3 and then decreased gradually to the hatching stage. Alteration of rm-cyp19b and rm-cyp19a gene expression was further analyzed in the brain and gonad by real-time RT-PCR 96 h after EDC exposure in hermaphrodites and secondary males. The brain aromatase rm-cyp19b gene was up-regulated in the brain after 4-nonylphenol (4-NP)-exposure, while the ovarian aromatase rm-cyp19a gene was significantly down-regulated in the gonad. In 300 microg/L 4-tert octylphenol (4-tert-OP), or 600 microg/L bisphenol A-exposed brain and gonad, both rm-cyp19b and rm-cyp19a genes were up-regulated. In the case of secondary males, the rm-cyp19b gene was highly expressed in

Expression of estrogen-related gene markers in breast cancer tissue predicts aromatase inhibitor responsiveness.

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Irene Moy

Full Text Available Aromatase inhibitors (AIs are the most effective class of drugs in the endocrine treatment of breast cancer, with an approximate 50% treatment response rate. Our objective was to determine whether intratumoral expression levels of estrogen-related genes are predictive of AI responsiveness in postmenopausal women with breast cancer. Primary breast carcinomas were obtained from 112 women who received AI therapy after failing adjuvant tamoxifen therapy and developing recurrent breast cancer. Tumor ERα and PR protein expression were analyzed by immunohistochemistry (IHC. Messenger RNA (mRNA levels of 5 estrogen-related genes-AKR1C3, aromatase, ERα, and 2 estradiol/ERα target genes, BRCA1 and PR-were measured by real-time PCR. Tumor protein and mRNA levels were compared with breast cancer progression rates to determine predictive accuracy. Responsiveness to AI therapy-defined as the combined complete response, partial response, and stable disease rates for at least 6 months-was 51%; rates were 56% in ERα-IHC-positive and 14% in ERα-IHC-negative tumors. Levels of ERα, PR, or BRCA1 mRNA were independently predictive for responsiveness to AI. In cross-validated analyses, a combined measurement of tumor ERα and PR mRNA levels yielded a more superior specificity (36% and identical sensitivity (96% to the current clinical practice (ERα/PR-IHC. In patients with ERα/PR-IHC-negative tumors, analysis of mRNA expression revealed either non-significant trends or statistically significant positive predictive values for AI responsiveness. In conclusion, expression levels of estrogen-related mRNAs are predictive for AI responsiveness in postmenopausal women with breast cancer, and mRNA expression analysis may improve patient selection.

Physical activity and biological maturation: a systematic review

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Eliane Denise Araújo Bacil

2015-03-01

Full Text Available OBJECTIVE: To analyze the association between physical activity (PA and biological maturation in children and adolescents. DATA SOURCE: We performed a systematic review in April 2013 in the electronic databases of PubMed/MEDLINE, SportDiscus, Web of Science and LILACS without time restrictions. A total of 628 potentially relevant articles were identified and 10 met the inclusion criteria for this review: cross-sectional or longitudinal studies, published in Portuguese, English or Spanish, with schoolchildren aged 9-15 years old of both genders. DATA SYNTHESIS: Despite the heterogeneity of the studies, there was an inverse association between PA and biological maturation. PA decreases with increased biological and chronological age in both genders. Boys tend to be more physically active than girls; however, when controlling for biological age, the gender differences disappear. The association between PA and timing of maturation varies between the genders. Variation in the timing of biological maturation affects the tracking of PA in early adolescent girls. This review suggests that mediators (BMI, depression, low self-esteem, and concerns about body weight can explain the association between PA and biological maturation. CONCLUSIONS: There is an association between PA and biological maturation. PA decreases with increasing biological age with no differences between genders. As for the timing of biological maturation, this association varies between genders.

Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: The BATMAN Trial.

Science.gov (United States)

Lomax, Anna J; Yee Yap, Saw; White, Karen; Beith, Jane; Abdi, Ehtesham; Broad, Adam; Sewak, Sanjeev; Lee, Chooi; Sambrook, Philip; Pocock, Nicholas; Henry, Margaret J; Yeow, Elaine G; Bell, Richard

2013-12-01

Postmenopausal women on aromatase inhibitors (AI) are at risk of aromatase inhibitor-associated bone loss (AIBL) and fractures. In 2005 Osteoporosis Australia proposed an algorithm for bisphosphonate intervention. Three hundred and three postmenopausal women with early breast cancer (EBC) were enrolled (osteoporotic, n=25; osteopaenic, n=146; normal bone mineral density (BMD), n=126). Weekly alendronate (70 mg) treatment efficacy as triggered by the algorithm in preventing bone loss was evaluated. All patients received anastrozole (1 mg daily), calcium and vitamin D. All osteoporotic patients received alendronate at baseline. Eleven out of the 146 (7.5%) osteopaenic patients commenced alendronate within 18 months of participation and eleven commenced after. One hundred and twenty four out of the 146 (84.9%) osteopaenic patients and all 126 with normal baseline BMD did not trigger the algorithm. At three years, lumbar spine mean BMD increased (15.6%, p<0.01) in the osteoporotic group. BMD in the osteopaenic group with early intervention significantly increased at three years (6.3%, p=0.02). No significant change was seen in the late intervention group. No change was observed in those with osteopaenia without alendronate. There was a significant drop in lumbar spine (-5.4%) and hip (-4.5%) mean BMD, in the normal BMD group, none of whom received alendronate. Fracture data will be presented. In postmenopausal women with endocrine-responsive EBC, BMD improved over time when a bisphosphonate is administered with anastrozole in osteoporotic patients using an osteoporosis schedule. Subjects with normal baseline BMD experienced the greatest BMD loss, although none became osteoporotic.

Loranthus micranthus Linn.: Biological Activities and Phytochemistry

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Soheil Zorofchian Moghadamtousi

2013-01-01

Full Text Available Loranthus micranthus Linn. is a medicinal plant from the Loranthaceae family commonly known as an eastern Nigeria species of the African mistletoe and is widely used in folkloric medicine to cure various ailments and diseases. It is semiparasitic plant because of growing on various host trees and shrubs and absorbing mineral nutrition and water from respective host. Hence, the phytochemicals and biological activities of L. micranthus demonstrated strong host and harvesting period dependency. The leaves have been proved to possess immunomodulatory, antidiabetic, antimicrobial, antihypertensive, antioxidant, antidiarrhoeal, and hypolipidemic activities. This review summarizes the information and findings concerning the current knowledge on the biological activities, pharmacological properties, toxicity, and chemical constituents of Loranthus micranthus.

Polysaccharides from Traditional Chinese Medicines: Extraction, Purification, Modification, and Biological Activity.

Science.gov (United States)

Chen, Yun; Yao, Fangke; Ming, Ke; Wang, Deyun; Hu, Yuanliang; Liu, Jiaguo

2016-12-13

Traditional Chinese Medicine (TCM) has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. Polysaccharides from TCMs exhibit a wide range of biological activities in terms of immunity- modifying, antiviral, anti-inflammatory, anti-oxidative, and anti-tumor properties. With their widespread biological activities, polysaccharides consistently attract scientist's interests, and the studies often concentrate on the extraction, purification, and biological activity of TCM polysaccharides. Currently, numerous studies have shown that the modification of polysaccharides can heighten or change the biological activities, which is a new angle of polysaccharide research. This review highlights the current knowledge of TCM polysaccharides, including their extraction, purification, modification, and biological activity, which will hopefully provide profound insights facilitating further research and development.

Polysaccharides from Traditional Chinese Medicines: Extraction, Purification, Modification, and Biological Activity

Directory of Open Access Journals (Sweden)

Yun Chen

2016-12-01

Full Text Available Traditional Chinese Medicine (TCM has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. Polysaccharides from TCMs exhibit a wide range of biological activities in terms of immunity- modifying, antiviral, anti-inflammatory, anti-oxidative, and anti-tumor properties. With their widespread biological activities, polysaccharides consistently attract scientist's interests, and the studies often concentrate on the extraction, purification, and biological activity of TCM polysaccharides. Currently, numerous studies have shown that the modification of polysaccharides can heighten or change the biological activities, which is a new angle of polysaccharide research. This review highlights the current knowledge of TCM polysaccharides, including their extraction, purification, modification, and biological activity, which will hopefully provide profound insights facilitating further research and development.

Effect of gamma irradiation on biological activity of thyrotropin

Energy Technology Data Exchange (ETDEWEB)

Strbak, V; Macho, L; Sedlak, J; Hromadova, M

1976-03-01

The biological activity of thyrotropin (TSH) was tested after sterilization by 0.5 and 12.5 Mrad of gamma irradiation. It was found that the biological activity (McKenzie's assay) of TSH irradiated in dry state was not affected during the first month after sterilization by doses of 0.5 and 2.5 Mrad. However, substantial decrease of TSH biological activity was observed 3 to 5 months after the irradiation, the lower activity being after the former dose. The irradiation of TSH by 12.5 Mrad in dry state and by 0.5 and 2.5 Mrad in solution resulted in a decrease of biological activity already during first month. The structural changes in the molecule of TSH were apparently not very extensive, since a decrease of disulfide bonds from 0.96 to 0.77 M per 1M of TSH was found immediately after the irradiation, while uv absorbancy and electrophoretic mobility on polyacrylamide gel electrophoresis were unaffected. These changes were followed by the decrease of TSH stability during storage in dry state. It is hypothesized that TSH molecule may be affected in ..beta.. subunit or in its connection with ..cap alpha...

Effect of gamma irradiation on biological activity of thyrotropin

International Nuclear Information System (INIS)

Strbak, V.; Macho, L.; Sedlak, J.; Hromadova, M.

1976-01-01

The biological activity of thyrotropin (TSH) was tested after sterilization by 0.5 and 12.5 Mrad of gamma radiation. It was found that the biological activity (McKenzie's assay) of TSH irradiated in dry state was not affected during the first month after sterilization by doses of 0.5 and 2.5 Mrad. However, substantial decrease of TSH biological activity was observed 3 to 5 months after the irradiation, the lower activity after the 0.5 Mrad dose. The irradiation of TSH by 12.5 Mrad in dry state and by 0.5 and 2.5 Mrad in solution resulted in decreased biological activity already during the first month. The structural changes in the TSH molecule were apparently not very extensive, as a decrease of disulfide bonds from 0.96 to 0.77 M per 1 M of TSH was found immediately after the irradiation, while UV absorbancy and electrophoretic mobility on polyacrylamide gel electrophoresis were unaffected. These changes were followed by a decrease of TSH stability during storage in dry state. It is hypothesized that a TSH molecule may be affected in a β subunit or in its connection with α. (author)

The time since last menstrual period is important as a clinical predictor for non-steroidal aromatase inhibitor-related arthralgia.

Science.gov (United States)

Kanematsu, Miyuki; Morimoto, Masami; Honda, Junko; Nagao, Taeko; Nakagawa, Misako; Takahashi, Masako; Tangoku, Akira; Sasa, Mitsunori

2011-10-10

The clinical predictors of aromatase inhibitor-related arthralgia (AIA), a drug-related adverse reaction of aromatase inhibitors (AIs), remain unclear. AIA was prospectively surveyed every 4 months in 328 postmenopausal breast cancer patients administered a non-steroidal AI (anastrozole). Various clinicopathological parameters were recorded and analyzed (chi-square test, Fisher's exact test and logistic regression analysis). The mean observation period was 39.9 months. AIA manifested in 114 patients (34.8%), with peaks of onset at 4 (33.7%) and 8 months (11.4%) after starting AI administration. Some cases manifested even after 13 months. AIA tended to occur in younger patients (incidences of 46.3%, 37.4% and 28.0% for ages of 65 years, respectively (p = 0.063)) and decreased significantly with the age at menarche (53.3%, 35.3% and 15.4% for 15 years, respectively (p = 0.036)). The incidences were 45.1%, 46.3 and 25.1% for the time since the last menstrual period (LMP) 10 years, being significantly lower at > 10 years (p time since LMP > 10-year group versus the time since LMP became shorter ( 10 years since LMP. When the time since LMP was short, the onset of AIA was significantly earlier after starting AI administration.

Transport of biologically active material in laser cutting.

Science.gov (United States)

Frenz, M; Mathezloic, F; Stoffel, M H; Zweig, A D; Romano, V; Weber, H P

1988-01-01

The transport of biologically active material during laser cutting with CO2 and Er lasers is demonstrated. This transport mechanism removes particles from the surface of gelatin, agar, and liver samples into the depth of the laser-formed craters. The transport phenomenon is explained by a contraction and condensation of enclosed hot water vapor. We show by cultivating transported bacteria in agar that biological particles can survive the shock of the transport. Determination of the numbers of active cells evidences a more pronounced activity of the cultivated bacteria after impact with an Er laser than with a CO2 laser.

Systems Biology Graphical Notation: Activity Flow language Level 1 Version 1.2.

Science.gov (United States)

Mi, Huaiyu; Schreiber, Falk; Moodie, Stuart; Czauderna, Tobias; Demir, Emek; Haw, Robin; Luna, Augustin; Le Novère, Nicolas; Sorokin, Anatoly; Villéger, Alice

2015-09-04

The Systems Biological Graphical Notation (SBGN) is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD), Entity Relationship (ER) and Activity Flow (AF), allow for the representation of different aspects of biological and biochemical systems at different levels of detail. The SBGN Activity Flow language represents the influences of activities among various entities within a network. Unlike SBGN PD and ER that focus on the entities and their relationships with others, SBGN AF puts the emphasis on the functions (or activities) performed by the entities, and their effects to the functions of the same or other entities. The nodes (elements) describe the biological activities of the entities, such as protein kinase activity, binding activity or receptor activity, which can be easily mapped to Gene Ontology molecular function terms. The edges (connections) provide descriptions of relationships (or influences) between the activities, e.g., positive influence and negative influence. Among all three languages of SBGN, AF is the closest to signaling pathways in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.

Biological Activity of Curcuminoids Isolated from Curcuma longa

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Simay Çıkrıkçı

2008-04-01

Full Text Available Curcumin is the most important fraction of turmeric which is responsible for its biological activity. In this study, isolation and biological assessment of turmeric and curcumin have been discussed against standard bacterial and mycobacterial strains such as E.coli , S.aureus, E.feacalis, P.aeuroginosa, M.smegmatis, M.simiae, M.kansasii, M. terrae, M.szulgai and the fungi Candida albicans. The antioxidant activity of curcumin and turmeric were also determined by the CUPRAC method.

Using Active Learning to Teach Concepts and Methods in Quantitative Biology.

Science.gov (United States)

Waldrop, Lindsay D; Adolph, Stephen C; Diniz Behn, Cecilia G; Braley, Emily; Drew, Joshua A; Full, Robert J; Gross, Louis J; Jungck, John A; Kohler, Brynja; Prairie, Jennifer C; Shtylla, Blerta; Miller, Laura A

2015-11-01

This article provides a summary of the ideas discussed at the 2015 Annual Meeting of the Society for Integrative and Comparative Biology society-wide symposium on Leading Students and Faculty to Quantitative Biology through Active Learning. It also includes a brief review of the recent advancements in incorporating active learning approaches into quantitative biology classrooms. We begin with an overview of recent literature that shows that active learning can improve students' outcomes in Science, Technology, Engineering and Math Education disciplines. We then discuss how this approach can be particularly useful when teaching topics in quantitative biology. Next, we describe some of the recent initiatives to develop hands-on activities in quantitative biology at both the graduate and the undergraduate levels. Throughout the article we provide resources for educators who wish to integrate active learning and technology into their classrooms. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Ficus carica L. (Moraceae: Phytochemistry, Traditional Uses and Biological Activities

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Shukranul Mawa

2013-01-01

Full Text Available This paper describes the botanical features of Ficus carica L. (Moraceae, its wide variety of chemical constituents, its use in traditional medicine as remedies for many health problems, and its biological activities. The plant has been used traditionally to treat various ailments such as gastric problems, inflammation, and cancer. Phytochemical studies on the leaves and fruits of the plant have shown that they are rich in phenolics, organic acids, and volatile compounds. However, there is little information on the phytochemicals present in the stem and root. Reports on the biological activities of the plant are mainly on its crude extracts which have been proven to possess many biological activities. Some of the most interesting therapeutic effects include anticancer, hepatoprotective, hypoglycemic, hypolipidemic, and antimicrobial activities. Thus, studies related to identification of the bioactive compounds and correlating them to their biological activities are very useful for further research to explore the potential of F. carica as a source of therapeutic agents.

Hypothalamic-pituitary-ovarian axis during infancy, early and late prepuberty in an aromatase-deficient girl who is a compound heterocygote for two new point mutations of the CYP19 gene.

Science.gov (United States)

Belgorosky, Alicia; Pepe, Carolina; Marino, Roxana; Guercio, Gabriela; Saraco, Nora; Vaiani, Elisa; Rivarola, Marco A

2003-11-01

A loss of function mutation of the CYP19 aromatase gene leads to excess circulating androgens in the fetus and in the mother, resulting in ambiguous genitalia in the female fetus. Later on, lack of aromatase is responsible for sexual infantilism, primary amenorrhea, tall stature, and multicystic ovaries, even in preadolescent girls. Up to now, 11 CYP19 aromatase point mutations and 10 well-documented cases have been reported. In the present case, we are reporting the clinical and hormonal follow-up, from birth to 7 yr of age, of an affected girl with ambiguous genitalia. Gene analysis showed that she was a compound heterozygote for two new CYP19 aromatase point mutations. In the father's allele, there was a consensus 5' splice donor sequence mutation, GAA-AAA at cDNA position bp 655 in exon 5, which probably results in a cryptic donor site. In the mother's allele, there was a base A deletion in exon 9 (Delta A GLU 412X), causing a frame shift mutation, and a stop codon after 98 bp (33 codons) downstream, altering the critical heme-binding region. Basal serum LH and FSH levels were high at 8 d of age (42.9 and 51.3 U/liter), 26 d of age (76.2 and 119 U/liter), and 60 d of age (58.7 and 150 U/liter, respectively). Both gonadotropins dropped dramatically between the second and fifth months of age (to 1.79 and 14.9 U/liter) but remained higher than in normal control girls (0.64 and 8.5 U/liter, respectively). Serum testosterone (T) and androstenedione (Delta(4)A) levels were high during the first month, but Delta(4)A was normal at 2 months of age. However, at 5 months of age, along with significant decrements of serum LH and FSH levels and increments in serum Delta(4)A and T levels, a large ovarian cyst was removed from each gonad. Relatively high levels of T [27.3 ng/ml (94.6 nmol/liter); control, 34.9 ng/ml (121 nmol/liter)], but not of estradiol [1.8 ng/ml (6.6 nmol/liter); control 62.9 ng/ml (231 nmol/liter)], and a high T/estradiol ratio [15.2; control < 1] were

A Conceptual Framework for Organizing Active Learning Experiences in Biology Instruction

Science.gov (United States)

Gardner, Joel; Belland, Brian R.

2012-01-01

Introductory biology courses form a cornerstone of undergraduate instruction. However, the predominantly used lecture approach fails to produce higher-order biology learning. Research shows that active learning strategies can increase student learning, yet few biology instructors use all identified active learning strategies. In this paper, we…

Use of aromatase inhibitors to treat endometriosis-related pain symptoms: a systematic review

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Venturini Pier L

2011-06-01

Full Text Available Abstract This systematic review aims to assess the efficacy of aromatase inhibitors (AIs in treating pain symptoms caused by endometriosis. A comprehensive literature search was conducted to identify all the published studies evaluating the efficacy of type II nonsteroidal aromatase inhibitors (anastrozole and letrozole in treating endometriosis-related pain symptoms. The MEDLINE, EMBASE, PubMed, and SCOPUS databases and the Cochrane System Reviews were searched up to October 2010. This review comprises of the results of 10 publications fitting the inclusion criteria; these studies included a total of 251 women. Five studies were prospective non-comparative, four were randomized controlled trials (RCTs and one was a prospective patient preference trial. Seven studies examined the efficacy of AIs in improving endometriosis-related pain symptoms, whilst three RCTs investigated the use of AIs as post-operative therapy in preventing the recurrence of pain symptoms after surgery for endometriosis. All the observational studies demonstrated that AIs combined with either progestogens or oral contraceptive pill reduce the severity of pain symptoms and improve quality of life. One patient preference study demonstrated that letrozole combined with norethisterone acetate is more effective in reducing pain and deep dyspareunia than norethisterone acetate alone. However, letrozole causes a higher incidence of adverse effects and does not improve patients' satisfaction or influence recurrence of symptoms after discontinuation of treatment. A RCT showed that combining letrozole with norethisterone acetate causes a lower incidence of adverse effects and lower discontinuation rate than combining letrozole with triptorelin. Two RCTs demonstrated that, after surgical treatment of endometriosis, the administration of AIs combined with gonadotropin releasing hormone analogue for 6 months reduces the risk of endometriosis recurrence when compared with gonadotropin

Hormonal enzymatic systems in normal and cancerous human breast: control, prognostic factors, and clinical applications.

Science.gov (United States)

Pasqualini, Jorge R; Chetrite, Gérard S

2012-04-01

The bioformation and transformation of estrogens and other hormones in the breast tissue as a result of the activity of the various enzymes involved attract particular attention for the role they play in the development and pathogenesis of hormone-dependent breast cancer. The enzymatic process concerns the aromatase, which transforms androgens into estrogens; the sulfatase, which hydrolyzes the biologically inactive sulfates to the active hormone; the 17β-hydroxysteroid dehydrogenases, which are involved in the interconversion estradiol/estrone or testosterone/androstenedione; hydroxylases, which transform estrogens into mitotic and antimitotic derivatives; and sulfotransferases and glucuronidases, which, respectively convert into the biologically inactive sulfates and glucuronides. These enzymatic activities are more intense in the carcinoma than in the normal tissue. Concerning aromatase, the application of antiaromatase agents has been largely developed in the treatment of breast cancer patients, with very positive results. Various studies have shown that the activity levels of these enzymes and their mRNA can be involved as interesting prognostic factors for breast cancer. In conclusion, the application of new antienzymatic molecules can open attractive perspectives in the treatment of hormone-dependent breast cancer.

Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels

DEFF Research Database (Denmark)

Bøtkjær, Jane Alrø; Jeppesen, Janni Vikkelsø; Wissing, Marie Louise

2015-01-01

To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological...... activity of PAPP-A in FF was evaluated....

Biological activities of some Xylooligosaccharides from ...

African Journals Online (AJOL)

Xylooligosaccharides (XOS's) exhibited considerable biological activities and be incorporated into many food products and in pharmaceutical and drug industry. XOS's were produced from xylose-containing polysaccharides (XPS's) obtained from natural, xylan-rich, agro-industrial wastes, i.e., corncobs and sugarcane ...

DNA methylation of the gonadal aromatase (cyp19a promoter is involved in temperature-dependent sex ratio shifts in the European sea bass.

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Laia Navarro-Martín

2011-12-01

Full Text Available Sex ratio shifts in response to temperature are common in fish and reptiles. However, the mechanism linking temperature during early development and sex ratios has remained elusive. We show in the European sea bass (sb, a fish in which temperature effects on sex ratios are maximal before the gonads form, that juvenile males have double the DNA methylation levels of females in the promoter of gonadal aromatase (cyp19a, the enzyme that converts androgens into estrogens. Exposure to high temperature increased the cyp19a promoter methylation levels of females, indicating that induced-masculinization involves DNA methylation-mediated control of aromatase gene expression, with an observed inverse relationship between methylation levels and expression. Although different CpGs within the sb cyp19a promoter exhibited different sensitivity to temperature, we show that the increased methylation of the sb cyp19a promoter, which occurs in the gonads but not in the brain, is not a generalized effect of temperature. Importantly, these effects were also observed in sexually undifferentiated fish and were not altered by estrogen treatment. Thus, methylation of the sb cyp19a promoter is the cause of the lower expression of cyp19a in temperature-masculinized fish. In vitro, induced methylation of the sb cyp19a promoter suppressed the ability of SF-1 and Foxl2 to stimulate transcription. Finally, a CpG differentially methylated by temperature and adjacent to a Sox transcription factor binding site is conserved across species. Thus, DNA methylation of the aromatase promoter may be an essential component of the long-sought-after mechanism connecting environmental temperature and sex ratios in vertebrate species with temperature-dependent sex determination.

Biological activity of SV40 DNA

International Nuclear Information System (INIS)

Abrahams, P.J.

1978-01-01

This thesis deals with a study on the biological activity of SV40 DNA. The transforming activity of SV40 DNA and DNA fragments is investigated in order to define as precisely as possible the area of the viral genome that is involved in the transformation. The infectivity of SV40 DNA is used to study the defective repair mechanisms of radiation damages of human xeroderma pigmentosum cells. (C.F.)

A Review of the Secondary Metabolites and Biological Activities of ...

African Journals Online (AJOL)

Review Article. A Review of the Secondary Metabolites and Biological. Activities of Tinospora crispa ... triterpenes have been isolated, some of which have also shown corresponding biological activities. The current review is an update on the .... were found to exhibit higher antioxidative potency than the synthetic antioxidant.

Inhibition of peripheral aromatization in baboons by an enzyme-activated aromatase inhibitor (MDL 18,962)

International Nuclear Information System (INIS)

Longcope, C.; Femino, A.; Johnston, J.O.

1988-01-01

The peripheral aromatization ([rho]BM) of androstenedione (A) and testosterone (T) was measured before and after administration of the aromatase inhibitor 10-(2 propynyl)estr-4-ene-3,17-dione (MDL-18,962) to five mature female baboons, Papio annubis. The measurements were made by infusing [3H]androstenedione/[14C]estrone or [3H]testosterone/[14C]estradiol for 3.5 h and collecting blood samples during the infusions and all urine for 96 h from the start of the infusion. Blood samples were analyzed for radioactivity as infused and product steroids, and the data were used to calculate MCRs. An aliquot of the pooled urine was analyzed for the glucuronides of estrone and estradiol and used to calculate the [rho]BM. MDL-18,962 was administered as a pulse in polyethylene glycol-400 (1-5 ml) either iv or via gastric tube 30 min before administration of the radiolabeled steroids. Control studies were done with and without polyethylene glycol-400 administration. When MDL-18,962 was given iv at 4 mg/kg, the aromatization of A was decreased 91.8 +/- 0.9% from the control value of 1.23 +/- 0.13% to 0.11 +/- 0.01%. At the same dose, aromatization of T was decreased 82.0 +/- 7.1%, from a control value of 0.20 +/- 0.03% to 0.037 +/- 0.018%. When MDL-18,962 was given iv at doses of 0.4, 0.1, 0.04, and 0.01 mg/kg, the values for aromatization of A were 0.16 +/- 0.03%, 0.18 +/- 0.06%, 0.37 +/- 11%, and 0.65 +/- 0.09%, respectively. The administration of MDL-18,962 via gastric tube at 4 mg/kg as a pulse decreased the aromatization of A from 1.35 +/- 0.06% to 0.43 +/- 0.12%, an inhibition of 67.2 +/- 10.7%. When administered via gastric tube daily for 5 days at 4 mg/kg, the aromatization of A fell from 1.35 +/- 0.06% to 0.063 +/- 0.003%, an inhibition of 84.4 +/- 0.5%

Neutron activation analysis of biological substances

International Nuclear Information System (INIS)

Ordogh, M.

1978-08-01

A Bowen cabbage sample was used as a reference material for the neutron activation studies, and the method was checked by the analysis of other biological substances (blood or serum etc.). For nondestructive measurements also some non-trace elements were determined in order to decide whether the activation analysis is a useful means for such measurements. The new activation analysis procedure was used for biomedical studies as, e.g., for trace element determination in body fluids, and for the analysis of inorganic components in air samples. (R.P.)

Functional Genomics for Epithelial-Mesenchymal Transition in Breast Cancer

Science.gov (United States)

2011-10-01

and aromatase activity are high compared to pre-meno- pausal plasma and tissue levels ( Pasqualini et al. 1996). LRH-1 has also been described as an...Hnf3beta, Hnf4alpha, and Hnf1alpha gene promoters. Journal of Biological Chemistry 276 13136–13144. (doi:10.1074/ jbc.M010737200) Pasqualini JR

Aromatase inhibitors, efficacy and metabolic risk in the treatment of postmenopausal women with early breast cancer

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Stefano Gonnelli

2008-12-01

Full Text Available Stefano Gonnelli1, Roberto Petrioli21Department of Internal Medicine, Endocrine-Metabolic Science and Biochemistry, University of Siena, Italy (Dir. R. Nuti.; 2Department of Human Pathology and Oncology, Medical Oncology Section, University of Siena, Italy (Dir. G. FranciniAbstract: The third-generation aromatase inhibitors (AIs, letrozole, anastrozole and exemestane, are becoming the first choice endocrine drugs for post-menopausal women with breast cancer, since they present greater efficacy when compared with tamoxifen in both adjuvant and metastatic setting. In particular, several large and well designed trials have suggested an important role for AIs in the adjuvant treatment of postmenopausal women with estrogen-receptor positive breast cancer either in the upfront, sequential or extended adjuvant mode. Overall, AIs are associated with a small but significant improvement in disease free survival. The expanding use of AIs in the treatment of early breast cancer means that individual patients will be exposed to the agents for longer durations, making it increasingly important to establish their long-term safety. This review focused on the effects of AIs on bone metabolism, serum lipids and cardiovascular risk. AIs have adverse effects on bone turnover with a reduction of bone mineral density and an increase in the rate of fragility fractures. With respect to tamoxifen AIs present lower thrombotic risk and a less favorable impact on lipid profile, whereas the true effects on cardiovascular risk still remain to be clarified. An adequate monitoring of bone mineral density (BMD and lipid profile could be recommended for post-menopausal women candidate to AIs.Keywords: breast cancer, aromatase inhibitors, bone loss, lipids, cardiovascular risk

A Review on Phytoconstituents and Biological activities of Cuscuta species.

Science.gov (United States)

Ahmad, Ateeque; Tandon, Sudeep; Xuan, Tran Dang; Nooreen, Zulfa

2017-08-01

The genus Cuscuta belonging to the Cuscutaceae family comprises of about 100-170 species spread around the world. Although several species have been studied for their phytochemical characterization and biological activities but still many species are yet unexplored till date. Cuscuta are parasitic plants generally of yellow, orange, red or rarely green color. The Cuscuta species were reported rich in flavonoid and glycosidic constituents along with alkaloids, fatty acids, fixed oil, minerals, essential oil and others phytomolecules also etc. Flavonoids and other molecules of Cuscuta species were reported for different types of biological activities such as antiproliferative activity, antioxidant activity, anti-inflammatory, hepatoprotective, antimicrobial and anxiolytic activity, while some other flavonoids have exhibited potential antiviral and anticancer especially in ovarian and breast cancer activities. This review is an attempt to compile all the available data for the 24 different of Cuscuta species on the basis of different types of phytochemical constituents and biological studies as above. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The half-lives of biological activity of some pesticides in water

OpenAIRE

Kyaw Myint Oo,

2001-01-01

In the absence of analytical methods, the half-lives of biological activity of pesticides can be estimated by bioassays. To determine the half-lives of biological acivity of pesticides to fish, static bioassays were conducted in the laboratory with ten different formulations of pesticides using Labeo rohita as a bio-indicator. The half-lives of biological activity for ten different pesticides in soft water at pH 7.5 and 27░C, ranged from 4.6 days to 11.8 days. The half-life of biological acti...

Biological activity of selected plants with adaptogenic effect

Directory of Open Access Journals (Sweden)

Eva Ivanišová

2016-05-01

Full Text Available The aim of this study was to determine biological activity of plants with adaptogenic effect: Panax ginseng Mayer., Withania somnifera L., Eleuterococcus senticosus Rupr. et Maxim., Astragallus membranaceus Fisch. and Codonopsis pilosulae Franch. The antioxidant activity was detected by DPPH and phosphomolybdenum method, total polyphenol content with Folin – Ciocalteu reagent, flavonoids content by aluminium chloride method. The detection of antimicrobial activity was carried out by disc diffusion method against three species of Gram-negative bacteria: Escherichia coli CCM 3988, Salmonella enterica subsp. enterica CCM 3807, Yersinia enterocolitica CCM 5671 and two Gram-positive bacteria: Bacillus thuringiensis CCM 19, Stapylococcus aureus subsp. aureus CCM 2461. Results showed that plants with adaptogenic effect are rich for biologically active substances. The highest antioxidant activity by DPPH method was determined in the sample of Eleuterococcus senticosus (3.15 mg TEAC – Trolox equivalent antioxidant capacity per g of sample and by phosphomolybdenum method in the sample of Codonopsis pilosulae (188.79 mg TEAC per g of sample. In the sample of Panax ginseng was measured the highest content of total polyphenols (8.10 mg GAE – galic acid equivalent per g of sample and flavonoids (3.41 μg QE – quercetin equivalent per g of sample. All samples also showed strong antimicrobial activity with the best results in Panax ginseng and Withania somnifera in particular for species Yersinia enterocolitica CCM 5671 and Salmonella enterica subsp. enterica CCM 3807. The analyzed species of plant with high value of biological activity can be used more in the future, not only in food, but also in cosmetics and pharmaceutical industries.

Application of activation techniques to biological analysis

International Nuclear Information System (INIS)

Bowen, H.J.M.

1981-01-01

Applications of activation analysis in the biological sciences are reviewed for the period of 1970 to 1979. The stages and characteristics of activation analysis are described, and its advantages and disadvantages enumerated. Most applications involve activation by thermal neutrons followed by either radiochemical or instrumental determination. Relatively little use has been made of activation by fast neutrons, photons, or charged particles. In vivo analyses are included, but those based on prompt gamma or x-ray emission are not. Major applications include studies of reference materials, and the elemental analysis of plants, marine biota, animal and human tissues, diets, and excreta. Relatively little use of it has been made in biochemistry, microbiology, and entomology, but it has become important in toxicology and environmental science. The elements most often determined are Ag, As, Au, Br, Ca, Cd, Cl, Co, Cr, Cs, Cu, Fe, Hg, I, K, Mn, Mo, Na, Rb, Sb, Sc, Se, and Zn, while few or no determinations of B, Be, Bi, Ga, Gd, Ge, H, In, Ir, Li, Nd, Os, Pd, Pr, Pt, Re, Rh, Ru, Te, Tl, or Y have been made in biological materials

Biological activity and photostability of biflorin micellar nanostructures.

Science.gov (United States)

Santana, Edson R B; Ferreira-Neto, João P; Yara, Ricardo; Sena, Kêsia X F R; Fontes, Adriana; Lima, Cláudia S A

2015-05-13

Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in its roots a compound named biflorin, an o-naphthoquinone that shows activity against Gram-positive bacteria and fungi and also presents antitumor and antimetastatic activities. However, biflorin is hydrophobic and photosensitive. These properties make its application difficult. In this work we prepared biflorin micellar nanostructures looking for a more effective vehiculation and better preservation of the biological activity. Biflorin was obtained, purified and characterized by UV-Vis, infrared (IR) and 1H- and 13C-NMR. Micellar nanostructures of biflorin were then assembled with Tween 80®, Tween 20® and saline (0.9%) and characterized by UV-Vis spectroscopy and dynamic light scattering (DLS). The results showed that the micellar nanostructures were stable and presented an average size of 8.3 nm. Biflorin micellar nanostructures' photodegradation was evaluated in comparison with biflorin in ethanol. Results showed that the biflorin in micellar nanostructures was better protected from light than biflorin dissolved in ethanol, and also indicated that biflorin in micelles were efficient against Gram-positive bacteria and yeast species. In conclusion, the results showed that the micellar nanostructures could ensure the maintenance of the biological activity of biflorin, conferring photoprotection. Moreover, biflorin vehiculation in aqueous media was improved, favoring its applicability in biological systems.

Biological Activity and Photostability of Biflorin Micellar Nanostructures

Directory of Open Access Journals (Sweden)

Edson R. B. Santana

2015-05-01

Full Text Available Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in its roots a compound named biflorin, an o-naphthoquinone that shows activity against Gram-positive bacteria and fungi and also presents antitumor and antimetastatic activities. However, biflorin is hydrophobic and photosensitive. These properties make its application difficult. In this work we prepared biflorin micellar nanostructures looking for a more effective vehiculation and better preservation of the biological activity. Biflorin was obtained, purified and characterized by UV-Vis, infrared (IR and 1H- and 13C-NMR. Micellar nanostructures of biflorin were then assembled with Tween 80®, Tween 20® and saline (0.9% and characterized by UV-Vis spectroscopy and dynamic light scattering (DLS. The results showed that the micellar nanostructures were stable and presented an average size of 8.3 nm. Biflorin micellar nanostructures’ photodegradation was evaluated in comparison with biflorin in ethanol. Results showed that the biflorin in micellar nanostructures was better protected from light than biflorin dissolved in ethanol, and also indicated that biflorin in micelles were efficient against Gram-positive bacteria and yeast species. In conclusion, the results showed that the micellar nanostructures could ensure the maintenance of the biological activity of biflorin, conferring photoprotection. Moreover, biflorin vehiculation in aqueous media was improved, favoring its applicability in biological systems.

Biological activation of carbon filters.

Science.gov (United States)

Seredyńska-Sobecka, Bozena; Tomaszewska, Maria; Janus, Magdalena; Morawski, Antoni W

2006-01-01

To prepare biological activated carbon (BAC), raw surface water was circulated through granular activated carbon (GAC) beds. Biological activity of carbon filters was initiated after about 6 months of filter operation and was confirmed by two methods: measurement of the amount of biomass attached to the carbon and by the fluorescein diacetate (FDA) test. The effect of carbon pre-washing on WG-12 carbon properties was also studied. For this purpose, the nitrogen adsorption isotherms at 77K and Fourier transform-infrared (FT-IR) spectra analyses were performed. Moreover, iodine number, decolorizing power and adsorption properties of carbon in relation to phenol were studied. Analysis of the results revealed that after WG-12 carbon pre-washing its BET surface increased a little, the pH value of the carbon water extract decreased from 11.0 to 9.4, decolorizing power remained at the same level, and the iodine number and phenol adsorption rate increased. In preliminary studies of the ozonation-biofiltration process, a model phenol solution with concentration of approximately 10mg/l was applied. During the ozonation process a dose of 1.64 mg O(3)/mg TOC (total organic carbon) was employed and the contact time was 5 min. Four empty bed contact times (EBCTs) in the range of 2.4-24.0 min were used in the biofiltration experiment. The effectiveness of purification was measured by the following parameters: chemical oxygen demand (COD(Mn)), TOC, phenol concentration and UV(254)-absorbance. The parameters were found to decrease with EBCT.

Liposomal packaging generates Wnt protein with in vivo biological activity.

Directory of Open Access Journals (Sweden)

Nathan T Morrell

2008-08-01

Full Text Available Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context.

[BIOLOGICAL ACTIVITY OF ANTIMICROBIAL PEPTIDES FROM CHICKENS THROMBOCYTES].

Science.gov (United States)

Sycheva, M V; Vasilchenko, A S; Rogozhin, E A; Pashkova, T M; Popova, L P; Kartashova, O L

2016-01-01

Isolation and study of biological activity of antimicrobial peptides from chickens thrombocytes. Peptides from chickens thrombocytes, obtained by reverse-phase high-performance liquid chromatography method with stepped and linear gradients of concentration increase of the organic solvent were used in the study. Their antimicrobial activity was determined by microtitration method in broth; mechanism of biological effect--by using fluorescent spectroscopy method with DNA-tropic dyes. Individual fractions of peptides were isolated from chickens thrombocytes, that possess antimicrobial activity against Staphylococcus aureus P209 and Escherichia coli K12. A disruption of integrity of barrier structures of microorganisms under the effect of thrombocyte antimicrobial peptides and predominance of cells with damaged membrane in the population of E. coli was established. The data obtained on antimicrobial activity and mechanism of bactericidal effect of the peptide fractions from chickens thrombocytes isolated for the first time expand the understanding of functional properties of chickens thrombocytes and open a perspective for their further study with the aim of use as antimicrobial means.

Marine natural flavonoids: chemistry and biological activities.

Science.gov (United States)

Martins, Beatriz T; Correia da Silva, Marta; Pinto, Madalena; Cidade, Honorina; Kijjoa, Anake

2018-05-04

As more than 70% of the world's surface is covered by oceans, marine organisms offer a rich and unlimited resource of structurally diverse bioactive compounds. These organisms have developed unique properties and bioactive compounds that are, in majority of them, unparalleled by their terrestrial counterparts due to the different surrounding ecological systems. Marine flavonoids have been extensively studied in the last decades due to a growing interest concerning their promising biological/pharmacological activities. The most common classes of marine flavonoids are flavones and flavonols, which are mostly isolated from marine plants. Although most of flavonoids are hydroxylated and methoxylated, some marine flavonoids possess an unusual substitution pattern, not commonly found in terrestrial organisms, namely the presence of sulphate, chlorine, and amino groups. This review presents, for the first time in a systematic way, the structure, natural occurrence, and biological activities of marine flavonoids.

Monitoring Biological Activity at Geothermal Power Plants

Energy Technology Data Exchange (ETDEWEB)

Peter Pryfogle

2005-09-01

The economic impact of microbial growth in geothermal power plants has been estimated to be as high as $500,000 annually for a 100 MWe plant. Many methods are available to monitor biological activity at these facilities; however, very few plants have any on-line monitoring program in place. Metal coupon, selective culturing (MPN), total organic carbon (TOC), adenosine triphosphate (ATP), respirometry, phospholipid fatty acid (PLFA), and denaturing gradient gel electrophoresis (DGGE) characterizations have been conducted using water samples collected from geothermal plants located in California and Utah. In addition, the on-line performance of a commercial electrochemical monitor, the BIoGEORGE?, has been evaluated during extended deployments at geothermal facilities. This report provides a review of these techniques, presents data on their application from laboratory and field studies, and discusses their value in characterizing and monitoring biological activities at geothermal power plants.

Baltic cyanobacteria- A source of biologically active compounds

Digital Repository Service at National Institute of Oceanography (India)

Mazur-Marzec, H.; Błaszczyk, A.; Felczykowska, A.; Hohlfeld, N.; Kobos, J.; Toruńska-Sitarz, A.; PrabhaDevi; Montalva`o, S.; DeSouza, L.; Tammela, P.; Mikosik, A.; Bloch, S.; Nejman-Faleńczyk, B.; Węgrzyn, G.

cyanobacteria, enzyme activity, enzyme inhibitors, immunological activity, natural products, nonribosomal peptides, plant growth regulators 2 INTRODUCTION Cyanobacteria are Gram-negative bacteria which are widely distributed in many water bodies..., immunological, 4 antimicrobial and plant growth tests. The overall aim of the experiments was to identify strains showing the most promising biological activity for potential biotechnological application. MATERIALS AND METHODS Isolation, culture...

Comparison of pharmacokinetics of newly discovered aromatase inhibitors by a cassette microdosing approach in healthy Japanese subjects.

Science.gov (United States)

Kusuhara, Hiroyuki; Takashima, Tadayuki; Fujii, Hisako; Takashima, Tsutomu; Tanaka, Masaaki; Ishii, Akira; Tazawa, Shusaku; Takahashi, Kazuhiro; Takahashi, Kayo; Tokai, Hidekichi; Yano, Tsuneo; Kataoka, Makoto; Inano, Akihiro; Yoshida, Suguru; Hosoya, Takamitsu; Sugiyama, Yuichi; Yamashita, Shinji; Hojo, Taisuke; Watanabe, Yasuyoshi

2017-12-01

The aim of the present study is to investigate the pharmacokinetics of our newly developed aromatase inhibitors (cetrozole and TMD-322) in healthy subjects by a cassette microdose strategy. A cocktail of cetrozole and TMD-322 was administered intravenously or orally (1.98 μg for each drug) to six healthy volunteers in a crossover fashion. Anastrozole (1.98 μg) was also included in the oral cocktail. Total body clearance and bioavailability were 12.1 ± 7.1 mL/min/kg and 34.9 ± 32.3% for cetrozole, and 16.8 ± 3.5 mL/min/kg and 18.4 ± 12.2% for TMD-322, respectively. The area under the plasma concentration-time curves of cetrozole and TMD-322 after oral administration was markedly lower than that of anastrozole because of their high hepatic clearance. Two subjects out of six exhibited 4- and 17-fold larger exposure of cetrozole than the others following intravenous and oral administration, respectively. Such variation was not observed for TMD-322 and anastrozole. Extensive metabolism of cetrozole and TMD-322 was observed in the CYP2C19 expression system among the test CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). We report the first clinical investigation of our aromatase inhibitors by a cassette microdose strategy in healthy Japanese subjects. This strategy offers an optional approach for candidate selection as a phase zero study in drug development. Copyright © 2017. Published by Elsevier Ltd.

Aspartate and glutamate mimetic structures in biologically active compounds.

Science.gov (United States)

Stefanic, Peter; Dolenc, Marija Sollner

2004-04-01

Glutamate and aspartate are frequently recognized as key structural elements for the biological activity of natural peptides and synthetic compounds. The acidic side-chain functionality of both the amino acids provides the basis for the ionic interaction and subsequent molecular recognition by specific receptor sites that results in the regulation of physiological or pathophysiological processes in the organism. In the development of new biologically active compounds that possess the ability to modulate these processes, compounds offering the same type of interactions are being designed. Thus, using a peptidomimetic design approach, glutamate and aspartate mimetics are incorporated into the structure of final biologically active compounds. This review covers different bioisosteric replacements of carboxylic acid alone, as well as mimetics of the whole amino acid structure. Amino acid analogs presented include those with different distances between anionic moieties, and analogs with additional functional groups that result in conformational restriction or alternative interaction sites. The article also provides an overview of different cyclic structures, including various cycloalkane, bicyclic and heterocyclic analogs, that lead to conformational restriction. Higher di- and tripeptide mimetics in which carboxylic acid functionality is incorporated into larger molecules are also reviewed. In addition to the mimetic structures presented, emphasis in this article is placed on their steric and electronic properties. These mimetics constitute a useful pool of fragments in the design of new biologically active compounds, particularly in the field of RGD mimetics and excitatory amino acid agonists and antagonists.

Assessing Student Behaviors and Motivation for Actively Learning Biology

Science.gov (United States)

Moore, Michael Edward

Vision and Change states that one of the major changes in the way we design biology courses should be a switch in approach from teacher-centered learning to student-centered learning and identifies active learning as a recommended methods. Studies show performance benefits for students taking courses that use active learning. What is unknown is why active learning is such an effective instructional tool and the limits of this instructional method’s ability to influence performance. This dissertation builds a case in three steps for why active learning is an effective instructional tool. In step one, I assessed the influence of different types of active learning (clickers, group activities, and whole class discussions) on student engagement behavior in one semester of two different introductory biology courses and found that active learning positively influenced student engagement behavior significantly more than lecture. For step two, I examined over four semesters whether student engagement behavior was a predictor of performance and found participation (engagement behavior) in the online (video watching) and in-class course activities (clicker participation) that I measure were significant predictors of performance. In the third, I assessed whether certain active learning satisfied the psychological needs that lead to students’ intrinsic motivation to participate in those activities when compared over two semesters and across two different institutions of higher learning. Findings from this last step show us that student’s perceptions of autonomy, competency, and relatedness in doing various types of active learning are significantly higher than lecture and consistent across two institutions of higher learning. Lastly, I tie everything together, discuss implications of the research, and address future directions for research on biology student motivation and behavior.

A qualitative systematic review of the evidence base for non-cross-resistance between steroidal and non-steroidal aromatase inhibitors in metastatic breast cancer.

Science.gov (United States)

Beresford, M; Tumur, I; Chakrabarti, J; Barden, J; Rao, N; Makris, A

2011-04-01

The most effective sequence of tamoxifen and both steroidal (SAIs) and non-steroidal aromatase inhibitors (NSAIs) has been extensively studied in the adjuvant setting. However, treatments for women who have failed initial aromatase inhibitor therapy in the metastatic setting have received relatively little attention. A systematic review was undertaken to assess the use of SAIs and NSAIs in metastatic breast cancer. Medline, Embase and the Cochrane library were searched using free text and MeSH terms. Studies assessing the cross-resistance, efficacy and safety of SAIs and NSAIs for postmenopausal women with advanced metastatic breast cancer confirmed by histology/cytology were included. Patients had progressed/relapsed from previous adjuvant, first- or second-line aromatase inhibitor treatment and had undergone treatment with at least two regimens consisting of aminoglutethimide, anastrozole, letrozole and/or exemestane. Nine studies reported results for patients treated with an SAI after treatment failure with an NSAI. For SAI after NSAI, clinical benefit was the most frequently reported outcome. The clinical benefit for exemestane (SAI) after any NSAI failure or before treatment ranged from 12% (complete response not recorded, partial response 2%, stable disease 10%) to 55% (complete response 6%, partial response 13%, stable disease 35%) Survival outcomes were infrequently reported; four studies reported disease progression. The time to progression ranged from 3.7 to 5.2 months. Only one study reported a median overall survival with exemestane at 15.2 months. Only one study reported information for an NSAI after SAI and an NSAI followed by another NSAI. This review suggests that switching from an NSAI to an SAI is a reasonable option. This would be particularly important for patients who would probably respond to further endocrine manoeuvres; strongly oestrogen receptor-positive disease, non-visceral disease, a good prior response or a long duration of response

Exploring rhizosphere bacteria of Eichhornia crassipes for metal tolerance and biological activity

Digital Repository Service at National Institute of Oceanography (India)

PrabhaDevi; Gomez, S.; Ribeiro, M.; Deshpande, S.A.; Singh, K.S.; DeSouza, L.

Cl₃, They were further screened for antibiotic sensitivity and biological activity according to Kirby-Bauer disc diffusion method The MTB under metal stress condition showed significant biological activity against clinical pathogens, fouling...

Comparative study of biological activity of glutathione, sodium ...

African Journals Online (AJOL)

Glutathione (GSH) and sodium tungstate (Na2WO4) are important pharmacological agents. They provide protection to cells against cytotoxic agents and thus reduce their cytotoxicity. It was of interest to study the biological activity of these two pharmacological active agents. Different strains of bacteria were used and the ...

Biological Activities of Royal Jelly - Review

Directory of Open Access Journals (Sweden)

Crenguţa I. Pavel

2011-10-01

Full Text Available Royal jelly is a secretion product of the cephalic glands of nurse bees that has been used for centuries for itsextraordinary properties and health effects. This bibliographic study aims to review many of the scientific findingsand research that prove many of the remarkable various actions, effects and some uses of royal jelly. There are takeninto consideration numerous biological properties and effects of royal jelly: antioxidant, neurotrophic, hipoglicemiant, hipocholesterolemiant and hepatoprotective, hypotensive and blood pressure regulatory, antitumor, antibiotic, anti-inflammatory, immunomodulatory and anti-allergic, general tonic and antiaging. Royal jelly is one ofthe most studied bee products, but there still remains much to reveal about its biochemistry and biological activity infuture research for our health and life benefit.

Biological activity of antitumoural MGBG: the structural variable.

Science.gov (United States)

Marques, M P M; Gil, F P S C; Calheiros, R; Battaglia, V; Brunati, A M; Agostinelli, E; Toninello, A

2008-05-01

The present study aims at determining the structure-activity relationships (SAR's) ruling the biological function of MGBG (methylglyoxal bis(guanylhydrazone)), a competitive inhibitor of S-adenosyl-L-methionine decarboxylase displaying anticancer activity, involved in the biosynthesis of the naturally occurring polyamines spermidine and spermine. In order to properly understand its biochemical activity, MGBG's structural preferences at physiological conditions were ascertained, by quantum mechanical (DFT) calculations.

In vitro - in vivo correlations for endocrine activity of a mixture of currently used pesticides

Energy Technology Data Exchange (ETDEWEB)

Taxvig, Camilla, E-mail: camta@food.dtu.dk [Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg (Denmark); Hadrup, Niels; Boberg, Julie; Axelstad, Marta [Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg (Denmark); Bossi, Rossana [Department of Environmental Science, Aarhus University, DK-4000 Roskilde (Denmark); Bonefeld-Jørgensen, Eva Cecilie [Department of Public Health, University of Aarhus, DK-8000 Aarhus C (Denmark); Vinggaard, Anne Marie [Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg (Denmark)

2013-11-01

Two pesticide mixtures were investigated for potential endocrine activity. Mix 3 consisted of bitertanol, propiconazole, and cypermethrin, and Mix 5 included malathion and terbuthylazine in addition to the three pesticides in Mix 3. All five single pesticides and the two mixtures were investigated for their ability to affect steroidogenesis in vitro in H295R cells. The pesticides alone and both mixtures affected steroidogenesis with both mixtures causing increase in progesterone and decrease in testosterone. For Mix 5 an increase in estradiol was seen as well, indicating increased aromatase activity. The two mixtures were also investigated in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses. Decreased estradiol and reduced placental testosterone were seen in dams exposed to Mix 5. Also a significant increase in aromatase mRNA-levels in female adrenal glands was found for Mix5. However, either of the two mixtures showed any effects on fetal hormone levels in plasma or testis, or on anogenital distance. Overall, potential aromatase induction was found for Mix 5 both in vitro and in vivo, but not for Mix 3, an effect likely owed to terbuthylazine in Mix 5. However, the hormonal responses in vitro were only partly reflected in vivo, probably due to some toxicokinetic issues, as the pesticide levels in the amniotic fluid also were found to be negatively affected by the number of compounds present in the mixtures. Nonetheless, the H295R assay gives hints on conceivable interference with steroidogenesis, thus generating hypotheses on in vivo effects. - Highlights: • The study examines the endocrine disrupting potential of mixtures of pesticides. • All single pesticides and both mixtures affected steroidogenesis in vitro. • Potential aromatase induction was found for Mix 5 both in vitro and in vivo. • The hormonal responses in vitro were only partly reflected in vivo.

Parameters of biological activity in colorectal cancer

Czech Academy of Sciences Publication Activity Database

Svobodová, Š.; Topolčan, O.; Holubec jr., L.; Levý, M.; Pecen, Ladislav; Svačina, Š.

2011-01-01

Roč. 31, č. 1 (2011), s. 373-378 ISSN 0250-7005 Institutional research plan: CEZ:AV0Z10300504 Keywords : colorectal cancer * biological activity * prognosis * tumor markers * angiogenetic factors * metalloproteinases * adhesion molecules Subject RIV: FD - Oncology ; Hematology Impact factor: 1.725, year: 2011

Advanced biological activated carbon filter for removing pharmaceutically active compounds from treated wastewater.

Science.gov (United States)

Sbardella, Luca; Comas, Joaquim; Fenu, Alessio; Rodriguez-Roda, Ignasi; Weemaes, Marjoleine

2018-04-28

Through their release of effluents, conventional wastewater treatment plants (WWTPs) represent a major pollution point sources for pharmaceutically active compounds (PhACs) in water bodies. The combination of a biological activated carbon (BAC) filter coupled with an ultrafiltration (UF) unit was evaluated as an advanced treatment for PhACs removal at pilot scale. The BAC-UF pilot plant was monitored for one year. The biological activity of the biofilm that developed on the granular activated carbon (GAC) particles and the contribution of this biofilm to the overall removal of PhACs were evaluated. Two different phases were observed during the long-term monitoring of PhACs removal. During the first 9200 bed volumes (BV; i.e., before GAC saturation), 89, 78, 83 and 79% of beta-blockers, psychiatric drugs, antibiotics and a mix of other therapeutic groups were removed, respectively. The second phase was characterized by deterioration of the overall performances during the period between 9200 and 13,800 BV. To quantify the respective contribution of adsorption and biodegradation, a lab-scale setup was operated for four months and highlighted the essential role played by GAC in biofiltration units. Physical adsorption was indeed the main removal mechanism. Nevertheless, a significant contribution due to biological activity was detected for some PhACs. The biofilm contributed to the removal of 22, 25, 30, 32 and 35% of ciprofloxacin, bezafibrate, ofloxacin, azithromycin and sulfamethoxazole, respectively. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Biological activity of selected plants with adaptogenic effect

OpenAIRE

Eva Ivanišová; Miroslava Kačániová; Jana Petrová; Radka Staňková; Lucia Godočíková; Tomáš Krajčovič; Štefan Dráb

2016-01-01

The aim of this study was to determine biological activity of plants with adaptogenic effect: Panax ginseng Mayer., Withania somnifera L., Eleuterococcus senticosus Rupr. et Maxim., Astragallus membranaceus Fisch. and Codonopsis pilosulae Franch. The antioxidant activity was detected by DPPH and phosphomolybdenum method, total polyphenol content with Folin – Ciocalteu reagent, flavonoids content by aluminium chloride method. The detection of antimicrobial activity was carried out by disc diff...

Biologic activity of porphyromonas endodontalis complex lipids.

Science.gov (United States)

Mirucki, Christopher S; Abedi, Mehran; Jiang, Jin; Zhu, Qiang; Wang, Yu-Hsiung; Safavi, Kamran E; Clark, Robert B; Nichols, Frank C

2014-09-01

Periapical infections secondary to pulpal necrosis are associated with bacterial contamination of the pulp. Porphyromonas endodontalis, a gram-negative organism, is considered to be a pulpal pathogen. P. gingivalis is phylogenetically related to P. endodontalis and synthesizes several classes of novel complex lipids that possess biological activity, including the capacity to promote osteoclastogenesis and osteoclast activation. The purpose of this study was to extract and characterize constituent lipids of P. endodontalis and evaluate their capacity to promote proinflammatory secretory responses in the macrophage cell line, RAW 264.7, as well as their capacity to promote osteoclastogenesis and inhibit osteoblast activity. Constituent lipids of both organisms were fractionated by high-performance liquid chromatography and were structurally characterized using electrospray mass spectrometry or electrospray-mass spectrometry/mass spectrometry. The virulence potential of P. endodontalis lipids was then compared with known biologically active lipids isolated from P. gingivalis. P. endodontalis total lipids were shown to promote tumor necrosis factor alpha secretion from RAW 264.7 cells, and the serine lipid fraction appeared to account for the majority of this effect. P. endodontalis lipid preparations also increased osteoclast formation from RAW 264.7 cells, but osteoblast differentiation in culture was inhibited and appeared to be dependent on Toll-like receptor 2 expression. These effects underscore the importance of P. endodontalis lipids in promoting inflammatory and bone cell activation processes that could lead to periapical pathology. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The Importance of Spatiotemporal Information in Biological Motion Perception: White Noise Presented with a Step-like Motion Activates the Biological Motion Area.

Science.gov (United States)

Callan, Akiko; Callan, Daniel; Ando, Hiroshi

2017-02-01

Humans can easily recognize the motion of living creatures using only a handful of point-lights that describe the motion of the main joints (biological motion perception). This special ability to perceive the motion of animate objects signifies the importance of the spatiotemporal information in perceiving biological motion. The posterior STS (pSTS) and posterior middle temporal gyrus (pMTG) region have been established by many functional neuroimaging studies as a locus for biological motion perception. Because listening to a walking human also activates the pSTS/pMTG region, the region has been proposed to be supramodal in nature. In this study, we investigated whether the spatiotemporal information from simple auditory stimuli is sufficient to activate this biological motion area. We compared spatially moving white noise, having a running-like tempo that was consistent with biological motion, with stationary white noise. The moving-minus-stationary contrast showed significant differences in activation of the pSTS/pMTG region. Our results suggest that the spatiotemporal information of the auditory stimuli is sufficient to activate the biological motion area.

Biological activity of Stevia rebaudiana Bertoni and their relationship to health.

Science.gov (United States)

Ruiz-Ruiz, Jorge Carlos; Moguel-Ordoñez, Yolanda Beatriz; Segura-Campos, Maira Rubi

2017-08-13

The leaves of Stevia rebaudiana Bertoni has nutrients and phytochemicals, which make it an adequate source for the extraction and production of functional food ingredients. Preclinical and clinical studies suggest therapeutic and pharmacological applications for stevia and their extracts because they are not toxic and exhibit several biological activities. This review presents the biological activity of Stevia rebaudiana Bertoni and their relationship to antidiabetic, anticariogenic, antioxidant, hypotensive, antihypertensive, antimicrobial, anti-inflammatory and antitumor activities. Consumption and adverse effects were also reviewed.

New approaches to estimation of peat deposits for production of biologically active compounds

Science.gov (United States)

Stepchenko, L. M.; Yurchenko, V. I.; Krasnik, V. G.; Syedykh, N. J.

2009-04-01

It is known, that biologically active preparations from peat increase animals productivity as well as resistance against stress-factors and have adaptogeneous, antioxidant, immunomodulative properties. Optymal choice of peat deposits for the production of biologically active preparations supposes the detailed comparative analysis of peat properties from different deposits. For this the cadastre of peat of Ukraine is developed in the humic substances laboratory named after prof. Khristeva L.A. (Dnipropetrovsk Agrarian University, Ukraine). It based on the research of its physical and chemical properties, toxicity and biological activity, and called Biocadastre. The Biocadastre is based on the set of parameters, including the descriptions of physical and chemical properties (active acidity, degree of decomposition, botanical composition etc.), toxicity estimation (by parabyotyc, infusorial, inhibitor and other tests), biological activity indexes (growth-promoting, antioxidative, adaptogeneous, immunomodulative antistress and other actions). The blocks of Biocadastre indexes are differentiated, taking into account their use for creation the preparations for vegetable, animals and microorganisms. The Biocadastre will allow to choose the peat deposits, most suitable for the production of different biologically active preparations, both wide directed and narrow spectrum of action, depending on application fields (medicine, agriculture, veterinary medicine, microbiological industry, balneology, cosmetology).

Biologically Active Compounds of Plant Foods: Prospective Impact ...

African Journals Online (AJOL)

On the other hand, other biologically active compounds impair health by ... of essential elements through different mechanisms and giving astringent taste, odor, ... The health benefits of selected substances from Ethiopian food crops need to ...

Biological Activity of Ionic Liquids and Their Application in Pharmaceutics and Medicine.

Science.gov (United States)

Egorova, Ksenia S; Gordeev, Evgeniy G; Ananikov, Valentine P

2017-05-24

Ionic liquids are remarkable chemical compounds, which find applications in many areas of modern science. Because of their highly tunable nature and exceptional properties, ionic liquids have become essential players in the fields of synthesis and catalysis, extraction, electrochemistry, analytics, biotechnology, etc. Apart from physical and chemical features of ionic liquids, their high biological activity has been attracting significant attention from biochemists, ecologists, and medical scientists. This Review is dedicated to biological activities of ionic liquids, with a special emphasis on their potential employment in pharmaceutics and medicine. The accumulated data on the biological activity of ionic liquids, including their antimicrobial and cytotoxic properties, are discussed in view of possible applications in drug synthesis and drug delivery systems. Dedicated attention is given to a novel active pharmaceutical ingredient-ionic liquid (API-IL) concept, which suggests using traditional drugs in the form of ionic liquid species. The main aim of this Review is to attract a broad audience of chemical, biological, and medical scientists to study advantages of ionic liquid pharmaceutics. Overall, the discussed data highlight the importance of the research direction defined as "Ioliomics", studies of ions in liquids in modern chemistry, biology, and medicine.

Silychristin: Skeletal Alterations and Biological Activities

Czech Academy of Sciences Publication Activity Database

Biedermann, David; Buchta, M.; Holečková, Veronika; Sedlák, David; Valentová, Kateřina; Cvačka, Josef; Bednárová, Lucie; Křenková, Alena; Kuzma, Marek; Škuta, Ctibor; Peikerová, Žaneta; Bartůněk, Petr; Křen, Vladimír

2016-01-01

Roč. 79, č. 12 (2016), s. 3086-3092 ISSN 0163-3864 R&D Projects: GA ČR(CZ) GA15-03037S; GA MZd(CZ) NV16-27317A; GA MŠk LO1220; GA MŠk LM2015063; GA MŠk(CZ) LD15081 Institutional support: RVO:61388971 ; RVO:68378050 ; RVO:61388963 Keywords : Silychristin * skeletal alterations * biological activities Subject RIV: CC - Organic Chemistry Impact factor: 3.281, year: 2016

Simple glycolipids of microbes: Chemistry, biological activity and metabolic engineering

Directory of Open Access Journals (Sweden)

Ahmad Mohammad Abdel-Mawgoud

2018-03-01

Full Text Available Glycosylated lipids (GLs are added-value lipid derivatives of great potential. Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents, they have diverse biological activities with promising biomedical and cosmeceutical applications. Glycolipids, especially those of microbial origin, have interesting antimicrobial, anticancer, antiparasitic as well as immunomodulatory activities. Nonetheless, GLs are hardly accessing the market because of their high cost of production. We believe that experience of metabolic engineering (ME of microbial lipids for biofuel production can now be harnessed towards a successful synthesis of microbial GLs for biomedical and other applications. This review presents chemical groups of bacterial and fungal GLs, their biological activities, their general biosynthetic pathways and an insight on ME strategies for their production.

Biological activity of soils strongly polluted with sulfur

Energy Technology Data Exchange (ETDEWEB)

Krol, M; Maliszewska, W; Siuta, J

1972-01-01

Studies were carried out on soils strongly polluted with sulfur and acidified (to pH 1.4). The soils were subjected to an intensive liming. In field and pot experiments, the authors determined: the total quantity of bacteria, actinomycetes, fungi, azotobacter, nitrifiers, proteolytic activity of microorganisms, activity of ammonifiers and the number of sulfur-oxidizing and sulfate-reducing bacteria. It was found that intensive liming of sulfur-affected soils restored their biological activity. 8 references, 5 figures, 1 table.

Radiometallating antibodies and biologically active peptides

International Nuclear Information System (INIS)

Mercer-Smith, J.A.; Roberts, J.C.; Lewis, D.; Newmyer, S.L.; Schulte, L.D.; Burns, T.P.; Mixon, P.L.; Jeffery, A.L.; Schreyer, S.A.; Cole, D.A.; Figard, S.D.; Lennon, V.A.; Hayashi, M.; Lavallee, D.K.

1990-01-01

We have developed methods to radiolabel large molecules, using porphyrins as bifunctional chelating agents for radiometals. The porphyrins are substituted with an N-benzyl group to activate them for radiometallation under mild reaction conditions. Porphyrins that have on functional group for covalent attachment to other molecules cannot cause crosslinking. We have examined the labeling chemistry for antibodies, and we have also developed methods to label smaller biologically active molecules, such as autoantigenic peptides. The autoantigenic peptides, fragments of the acetylcholine receptor, are under investigation for myasthenia gravis research. The methods of covalent attachment of these bifunctional chelating agents to large molecules and the radiometallation chemistry will be discussed

Increase of antitumor activity of cisplatin using agonist of gonadotropin-realising hormone and inhibitor of aromatase on the model of ascites ovarian tumor.

Science.gov (United States)

Tkalia, I G; Vorobyova, L I; Grabovoy, A N; Svintsitsky, V S; Tarasova, T O; Lukyanova, N Y; Todor, I N; Chekhun, V F

2014-09-01

To study antitumor activity of triptorelin - agonist of gonadotropin-releasing hormone and exemestane - inhibitor of aromatase in monotherapy and in combination with cisplatin on the model of receptor-positive for estrogens and progesterone malignant ascites transplantable ovarian tumor (TOT), to assess therapeutic pathomorphosis and level of VEGF expression in tumor cells using diffe-rent combinations of cytostatics and hormonal drugs. 72 female Wistar rats, which underwent intraperitoneal transplantation of ascitic TOT, by 5·10(6) cells per animal, have been involved in the study. Rats were divided into 8 groups, 9 rats in each group. Histological study with assessment of therapeutic pathomorphosis in TOT and immunohistochemical study has been carried out. Survival of animals in the studied groups has been evaluated. Among animals treated in regimen of monotherapy, the most pronounced antiangiogenic activity in TOT has been observed on application of hormonal drugs (triptorelin - 39.4 ± 1.9 and exemestane - 33.9 ± 1.4%; р = 0.003), the highest grade of treatment pathomorphosis in TOT has been observed at treatment with cisplatin (11.7%; р = 0.001). Combination of triptorelin and exemestane has amplified antiangiogenic activity in TOT (12.2 ± 0.9%; р = 0.001), but has not significantly changed rates of pathomorphosis (22.1 ± 0.4%; р=0.005) and survival of animals (32.2%; р = 0.007) as compared with the same rates in rats treated with hormonal drugs in monotherapy. Significant correlation between VEGF expression and pathomorphosis has been established (relative part of viable tumor tissue (RPVTT)) in TOT (r = 0.712; р = 0.001), as well as between RPVTT and life-span of animals (r = -0.320; р = 0.007). However, lack of correlation between VEGF expression in cells of TOT and survival of rats has been determined (r = -0.194; р = 0.11). Combination of cytostatic agent with triptorelin or exemestane has demonstrated significantly high rates of therapeutic

Biologically active substances from Zanthoxylum capense(thumb.) Harv.

CSIR Research Space (South Africa)

Steyn, PS

1998-08-01

Full Text Available A chemical investigation into the composition of Zanthoxylum capense yielded several biologically active compounds, including pellitorine. A convenient HPLC method was developed to determine the presence of pellitorine in crude extracts from plants...

Biological/Genetic Regulation of Physical Activity Level: Consensus from GenBioPAC.

Science.gov (United States)

Lightfoot, J Timothy; DE Geus, Eco J C; Booth, Frank W; Bray, Molly S; DEN Hoed, Marcel; Kaprio, Jaakko; Kelly, Scott A; Pomp, Daniel; Saul, Michael C; Thomis, Martine A; Garland, Theodore; Bouchard, Claude

2018-04-01

Physical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors; however, a growing body of literature suggests that biological determinants play a significant role in regulating physical activity levels. For instance, physical activity level, measured in various manners, has a genetic component in both humans and nonhuman animal models. This consensus article, developed as a result of an American College of Sports Medicine-sponsored round table, provides a brief review of the theoretical concepts and existing literature that supports a significant role of genetic and other biological factors in the regulation of physical activity. Future research on physical activity regulation should incorporate genetics and other biological determinants of physical activity instead of a sole reliance on social and other environmental determinants.

On the mechanism of biological activation by tritium.

Science.gov (United States)

Rozhko, T V; Badun, G A; Razzhivina, I A; Guseynov, O A; Guseynova, V E; Kudryasheva, N S

2016-06-01

The mechanism of biological activation by beta-emitting radionuclide tritium was studied. Luminous marine bacteria were used as a bioassay to monitor the biological effect of tritium with luminescence intensity as the physiological parameter tested. Two different types of tritium sources were used: HTO molecules distributed regularly in the surrounding aqueous medium, and a solid source with tritium atoms fixed on its surface (tritium-labeled films, 0.11, 0.28, 0.91, and 2.36 MBq/cm(2)). When using the tritium-labeled films, tritium penetration into the cells was prevented. The both types of tritium sources revealed similar changes in the bacterial luminescence kinetics: a delay period followed by bioluminescence activation. No monotonic dependences of bioluminescence activation efficiency on specific radioactivities of the films were found. A 15-day exposure to tritiated water (100 MBq/L) did not reveal mutations in bacterial DNA. The results obtained give preference to a "non-genomic" mechanism of bioluminescence activation by tritium. An activation of the intracellular bioluminescence process develops without penetration of tritium atoms into the cells and can be caused by intensification of trans-membrane cellular processes stimulated by ionization and radiolysis of aqueous media. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biological activities of Curcuma longa L.

Directory of Open Access Journals (Sweden)

Araújo CAC

2001-01-01

Full Text Available There are several data in the literature indicating a great variety of pharmacological activities of Curcuma longa L. (Zingiberaceae, which exhibit anti-inflammatory, anti-human immunodeficiency virus, anti-bacteria, antioxidant effects and nematocidal activities. Curcumin is a major component in Curcuma longa L., being responsible for its biological actions. Other extracts of this plant has been showing potency too. In vitro, curcumin exhibits anti-parasitic, antispasmodic, anti-inflammatory and gastrointestinal effects; and also inhibits carcinogenesis and cancer growth. In vivo, there are experiments showing the anti-parasitic, anti-inflammatory potency of curcumin and extracts of C. longa L. by parenteral and oral application in animal models. In this present work we make an overview of the pharmacological activities of C. longa L., showing its importance.

Correlation between the dielectric properties and biological activities of human ex vivo hepatic tissue

International Nuclear Information System (INIS)

Wang, Hang; You, Fusheng; Fu, Feng; Dong, Xiuzhen; Shi, Xuetao; He, Yong; Yang, Min; Yan, Qingguo

2015-01-01

Dielectric properties are vital biophysical features of biological tissues, and biological activity is an index to ascertain the active state of tissues. This study investigated the potential correlation between the dielectric properties and biological activities of human hepatic tissue with prolonged ex vivo time through correlation and regression analyses. The dielectric properties of 26 cases of normal human hepatic tissue at 10 Hz to 100 MHz were measured from 15 min after isolation to 24 h at 37 °C with 90% humidity. Cell morphologies, including nucleus area (NA) and alteration rate of intercellular area (ICAR), were analyzed as indicators of biological activities. Conductivity, complex resistivity, and NA exhibited opposing changes 1 h after isolation. Relative permittivity and ex vivo time were not closely correlated (p > 0.05). The dielectric properties measured at low frequencies (i.e. <1 MHz) were more sensitive than those measured at high frequencies in reflecting the biological activity of ex vivo tissue. Highly significant correlations were found between conductivity, resistivity and the ex vivo time (p < 0.05) as well as conductivity and the cell morphology (p < 0.05). The findings indicated that establishing the correlation between the dielectric properties and biological activities of human hepatic tissue is of great significance for promoting the role of dielectric properties in biological science, particularly in human biology. (paper)

Protein stability and enzyme activity at extreme biological temperatures

International Nuclear Information System (INIS)

Feller, Georges

2010-01-01

Psychrophilic microorganisms thrive in permanently cold environments, even at subzero temperatures. To maintain metabolic rates compatible with sustained life, they have improved the dynamics of their protein structures, thereby enabling appropriate molecular motions required for biological activity at low temperatures. As a consequence of this structural flexibility, psychrophilic proteins are unstable and heat-labile. In the upper range of biological temperatures, thermophiles and hyperthermophiles grow at temperatures > 100 0 C and synthesize ultra-stable proteins. However, thermophilic enzymes are nearly inactive at room temperature as a result of their compactness and rigidity. At the molecular level, both types of extremophilic proteins have adapted the same structural factors, but in opposite directions, to address either activity at low temperatures or stability in hot environments. A model based on folding funnels is proposed accounting for the stability-activity relationships in extremophilic proteins. (topical review)

Biological activities of xanthatin from Xanthium strumarium leaves.

Science.gov (United States)

Nibret, Endalkachew; Youns, Mahamoud; Krauth-Siegel, R Luise; Wink, Michael

2011-12-01

The objective of the present work was to evaluate the biological activities of the major bioactive compound, xanthatin, and other compounds from Xanthium strumarium (Asteraceae) leaves. Inhibition of bloodstream forms of Trypanosoma brucei brucei and leukaemia HL-60 cell proliferation was assessed using resazurin as a vital stain. Xanthatin was found to be the major and most active compound against T. b. brucei with an IC(50) value of 2.63 µg/mL and a selectivity index of 20. The possible mode of action of xanthatin was further evaluated. Xanthatin showed antiinflammatory activity by inhibiting both PGE(2) synthesis (24% inhibition) and 5-lipoxygenase activity (92% inhibition) at concentrations of 100 µg/mL and 97 µg/mL, respectively. Xanthatin exhibited weak irreversible inhibition of parasite specific trypanothione reductase. Unlike xanthatin, diminazene aceturate and ethidium bromide showed strong DNA intercalation with IC(50) values of 26.04 µg/mL and 44.70 µg/mL, respectively. Substantial induction of caspase 3/7 activity in MIA PaCa-2 cells was observed after 6 h of treatment with 100 µg/mL of xanthatin. All these data taken together suggest that xanthatin exerts its biological activity by inducing apoptosis and inhibiting both PGE(2) synthesis and 5-lipoxygenase activity thereby avoiding unwanted inflammation commonly observed in diseases such as trypanosomiasis. Copyright © 2011 John Wiley & Sons, Ltd.

Biological activities of some Fluoroquinolones-metal complexes

African Journals Online (AJOL)

McRoy

Background: Metal ions play a vital role in the design of more biologically active drugs. Aim: The paper reviewed the .... 2H2O by direct reaction of copper(II) sulphate pentahydrate with ciprofloxacin in distilled water. ... membered ring and the chloride ion completes the seven coordination around the Ca2+ion.[37-39].

Effects of eight weeks of an alleged aromatase inhibiting nutritional supplement 6-OXO (androst-4-ene-3,6,17-trione on serum hormone profiles and clinical safety markers in resistance-trained, eugonadal males

Directory of Open Access Journals (Sweden)

Kreider Richard

2007-10-01

Full Text Available Abstract The purpose of this study was to determine the effects of 6-OXO, a purported nutritional aromatase inhibitor, in a dose dependent manner on body composition, serum hormone levels, and clinical safety markers in resistance trained males. Sixteen males were supplemented with either 300 mg or 600 mg of 6-OXO in a double-blind manner for eight weeks. Blood and urine samples were obtained at weeks 0, 1, 3, 8, and 11 (after a 3-week washout period. Blood samples were analyzed for total testosterone (TT, free testosterone (FT, dihydrotestosterone (DHT, estradiol, estriol, estrone, SHBG, leutinizing hormone (LH, follicle stimulating hormone (FSH, growth hormone (GH, cortisol, FT/estradiol (T/E. Blood and urine were also analyzed for clinical chemistry markers. Data were analyzed with two-way MANOVA. For all of the serum hormones, there were no significant differences between groups (p > 0.05. Compared to baseline, free testosterone underwent overall increases of 90% for 300 mg 6-OXO and 84% for 600 mg, respectively (p 0.05 and clinical safety markers were not adversely affected with ingestion of either supplement dose (p > 0.05. While neither of the 6-OXO dosages appears to have any negative effects on clinical chemistry markers, supplementation at a daily dosage of 300 mg and 600 mg for eight weeks did not completely inhibit aromatase activity, yet significantly increased FT, DHT, and T/E.

In vitro effects of diethylstilbestrol, genistein, 4-tert-butylphenol, and 4-tert-octylphenol on steroidogenic activity of isolated immature rat ovarian follicles

International Nuclear Information System (INIS)

Myllymaeki, Sari; Haavisto, Tapio; Vainio, Minna; Toppari, Jorma; Paranko, Jorma

2005-01-01

Isolated rat ovarian follicles grow and produce steroid hormones in vitro and so provide a good model for studying the effects of hormonally active compounds on follicular steroidogenesis. We have evaluated the effects of diethylstilbestrol (DES), genistein (GEN) and two alkylphenols, 4-tert-butylphenol (BP) and 4-tert-octylphenol (OP) on the growth, survival, and steroid hormone and cAMP production by isolated 14-day-old rat (Sprague-Dawley) ovarian follicles. During a 5-day culture, FSH was obligatory for follicle growth and increased estradiol and testosterone secretion in a dose-dependent manner. DES (10 -6 M) caused the strongest decline in estradiol and testosterone levels but did not have detectable effects on either cAMP production or aromatase enzyme activity. GEN caused a prominent decrease in cAMP and testosterone levels without significant changes in secreted estradiol. The latter, apparently, was due to a dose-dependent stimulation of aromatase enzyme activity in the presence of genistein. Both BP and OP decreased estradiol and testosterone secretion in a dose-dependent manner while no effect on aromatase activity was observed. OP, unlike BP, decreased forskolin-induced cAMP levels. Xenoestrogens at the used concentrations did not interfere with the growth and survival of the follicles. The results indicate that isolated ovarian follicles representing intact morphological and functional units offer a sensitive model system for elucidating the female-specific reproductive effects of environmental chemicals

Objectives of research activities in Biology Branch, Chalk River Nuclear Laboratories, 1976

International Nuclear Information System (INIS)

1977-03-01

The primary responsibility assigned to the Biology Branch within the framework of CRNL has been an active engagement in basic research related to the assessment of radiation hazards, particularly those to be expected after exposure to relatively low doses of radiation delivered at low dose-rates. The present group is characterized by a broad interest in the entire chain of events by which the initial radiation-induced changes in the living cell are translated into biological effects, with a special focus of attention on the mechanisms by which the initial damage can be largely repaired and by which the risks to man are modified under different circumstances. The basic concepts in radiation biology and risk estimates are reviewed in the light of recent literature on these topics. The current and proposed research activities of the Biology Branch are described. General and specific recommendations for future activities are given. (author)

Ethnobotany, chemistry, and biological activities of the genus Tithonia (Asteraceae).

Science.gov (United States)

Chagas-Paula, Daniela A; Oliveira, Rejane B; Rocha, Bruno A; Da Costa, Fernando B

2012-02-01

The genus Tithonia is an important source of diverse natural products, particularly sesquiterpene lactones, diterpenes, and flavonoids. The collected information in this review attempts to summarize the recent developments in the ethnobotany, biological activities, and secondary metabolite chemistry of this genus. More than 100 structures of natural products from Tithonia are reported in this review. The species that has been most investigated in this genus is T. diversifolia, from which ca. 150 compounds were isolated. Biological studies are described to evaluate the anti-inflammatory, analgesic, antimalarial, antiviral, antidiabetic, antidiarrhoeal, antimicrobial, antispasmodic, vasorelaxant, cancer-chemopreventive, cytotoxic, toxicological, bioinsecticide, and repellent activities. A few of these studies have been carried out with isolated compounds from Tithonia species, but the majority has been conducted with different extracts. The relationship between the biological activity and the toxicity of compounds isolated from the plants of this genus as well as T. diversifolia extracts still remains unclear, and mechanisms of action remain to be determined. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

Genomic risk prediction of aromatase inhibitor-related arthralgia in patients with breast cancer using a novel machine-learning algorithm.

Science.gov (United States)

Reinbolt, Raquel E; Sonis, Stephen; Timmers, Cynthia D; Fernández-Martínez, Juan Luis; Cernea, Ana; de Andrés-Galiana, Enrique J; Hashemi, Sepehr; Miller, Karin; Pilarski, Robert; Lustberg, Maryam B

2018-01-01

Many breast cancer (BC) patients treated with aromatase inhibitors (AIs) develop aromatase inhibitor-related arthralgia (AIA). Candidate gene studies to identify AIA risk are limited in scope. We evaluated the potential of a novel analytic algorithm (NAA) to predict AIA using germline single nucleotide polymorphisms (SNP) data obtained before treatment initiation. Systematic chart review of 700 AI-treated patients with stage I-III BC identified asymptomatic patients (n = 39) and those with clinically significant AIA resulting in AI termination or therapy switch (n = 123). Germline DNA was obtained and SNP genotyping performed using the Affymetrix UK BioBank Axiom Array to yield 695,277 SNPs. SNP clusters that most closely defined AIA risk were discovered using an NAA that sequentially combined statistical filtering and a machine-learning algorithm. NCBI PhenGenI and Ensemble databases defined gene attribution of the most discriminating SNPs. Phenotype, pathway, and ontologic analyses assessed functional and mechanistic validity. Demographics were similar in cases and controls. A cluster of 70 SNPs, correlating to 57 genes, was identified. This SNP group predicted AIA occurrence with a maximum accuracy of 75.93%. Strong associations with arthralgia, breast cancer, and estrogen phenotypes were seen in 19/57 genes (33%) and were functionally consistent. Using a NAA, we identified a 70 SNP cluster that predicted AIA risk with fair accuracy. Phenotype, functional, and pathway analysis of attributed genes was consistent with clinical phenotypes. This study is the first to link a specific SNP/gene cluster to AIA risk independent of candidate gene bias. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Physio-chemical evaluation and biological activity of Ajuga ...

African Journals Online (AJOL)

Physio-chemical evaluation and biological activity of Ajuga bracteosa wall and Viola odoroto Linn. Anwar Ali Shad, M. Zeeshan, Hina Fazal, Hamid Ullah Shah, Shabir Ahmed, Hasem Abeer, E. F. Abd_Allah, Riaz Ullah, Hamid Afridi, Akash tariq, Muhammad Adnan Asma ...

Students’ learning activities while studying biological process diagrams

NARCIS (Netherlands)

Kragten, M.; Admiraal, W.; Rijlaarsdam, G.

2015-01-01

Process diagrams describe how a system functions (e.g. photosynthesis) and are an important type of representation in Biology education. In the present study, we examined students’ learning activities while studying process diagrams, related to their resulting comprehension of these diagrams. Each

Occurrence, biological activity and synthesis of drimane sesquiterpenoids

NARCIS (Netherlands)

Jansen, B.J.M.; Groot, de Æ.

2004-01-01

In this review the names, structures and occurrence of all new drimanes and rearranged drimanes, which have been published between January 1990 and January 2003 have been collected. Subjects that have been treated are biosynthesis, analysis, biological activities, with special attention to cytotoxic

Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance.

Science.gov (United States)

Eriksen, Mette Brandt; Glintborg, Dorte; Nielsen, Michael Friberg Bruun; Jakobsen, Marianne Antonius; Brusgaard, Klaus; Tan, Qihua; Gaster, Michael

2014-09-05

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls. Glucose transport in myotubes was comparable in patients with PCOS vs. controls and was unchanged by testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that testosterone treatment of myotubes increases the aromatase and androgen receptor gene expression without affecting insulin sensitivity and if testosterone is implicated in muscular insulin resistance in PCOS, this is by and indirect mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of biology teachers' professional knowledge and cognitive activation on students' achievement

Science.gov (United States)

Förtsch, Christian; Werner, Sonja; von Kotzebue, Lena; Neuhaus, Birgit J.

2016-11-01

This study examined the effects of teachers' biology-specific dimensions of professional knowledge - pedagogical content knowledge (PCK) and content knowledge (CK) - and cognitively activating biology instruction, as a feature of instructional quality, on students' learning. The sample comprised 39 German secondary school teachers whose lessons on the topic neurobiology were videotaped twice. Teachers' instruction was coded with regard to cognitive activation using a rating manual. Multilevel path analysis results showed a positive significant effect of cognitive activation on students' learning and an indirect effect of teachers' PCK on students' learning mediated through cognitive activation. These findings highlight the importance of PCK in preservice biology teachers' education. Items of the rating manual may be used to provide exemplars of concrete teaching situations during university seminars for preservice teacher education or professional development initiatives for in-service teachers.

Assessing Student Behaviors and Motivation for Actively Learning Biology

Science.gov (United States)

Moore, Michael Edward

2017-01-01

Vision and Change states that one of the major changes in the way we design biology courses should be a switch in approach from teacher-centered learning to student-centered learning and identifies active learning as a recommended methods. Studies show performance benefits for students taking courses that use active learning. What is unknown is…

Biological Activity Alterations of Human Amniotic Membrane Pre and Post Irradiation Tissue Banking.

Science.gov (United States)

Nemr, Waleed; Bashandy, A S; Araby, Eman; Khamiss, O

Innate immunity of Human Amniotic Membrane (HAM) and its highly active secretome that rich with various types of growth factors and anti-inflammatory substances proposed it as a promising material for many medical studies and applications. This study evaluate the biological activity of cultivated HAM pre and post tissue banking process in which freeze-dried HAM was sterilized by 25 KGray (kGy) dose of γ radiation. The HAM's antimicrobial activity, viability, growth of isolated human amniotic epithelial cells (HAECs), hematopoietic stimulation of co-cultivated murine bone marrow cells (mammalian model), scaffold efficiency for fish brain building up (non-mammalian model) and self re-epithelialization after trypsin denuding treatment were examined as supposed biological activity features. Native HAM revealed viability indications and was active to kill all tested microorganisms; 6 bacterial species (3 Gram-positive and 3 Gram-negative) and Candida albicans as a pathogenic fungus. Also, HAM activity promoted colony formation of murine hematopoietic cells, Tilapia nilotica brain fragment building-up and self re-epithelialization after trypsin treatment. In contrary, radiation-based tissue banking of HAM caused HAM cellular death and consequently lacked almost all of examined biological activity features. Viable HAM was featured with biological activity than fixed HAM prepared by irradiation tissue banking.

Detection of biologically active diterpenoic acids by Raman Spectroscopy

DEFF Research Database (Denmark)

Talian, Ivan; Orinak, Andrej; Efremov, Evtim V.

2010-01-01

Three poorly detectable, biologically active diterpenoic acids, kaurenoic, abietic, and gibberellic acid, were studied by using different modes of Raman spectroscopy. Because of their structural similarities, in the absence of strongly polarizable groups, conventional Raman spectroscopy is not su......Three poorly detectable, biologically active diterpenoic acids, kaurenoic, abietic, and gibberellic acid, were studied by using different modes of Raman spectroscopy. Because of their structural similarities, in the absence of strongly polarizable groups, conventional Raman spectroscopy...... few enhanced Raman lines. SERS spectra with 514-nm excitation with Ag colloids were also relatively weak. The best SERS spectrawere obtained with 785-nm excitation on a novel nanostructured substrate, 'black silicon' coated with a 400-nm gold layer. The spectra showed clear differences...

Biological activities of secondary metabolites of the order Zoanthids

Directory of Open Access Journals (Sweden)

Zahra Aminikhoei

2015-11-01

Full Text Available The phylum Cnidaria is a large, diverse and ecologically important group of marine invertebrates, which produce powerful toxins and venoms. The number of marine natural product from cnidarians isolated from class Anthozoa. Among the Anthozoa, the order of zoanthids are sessile, clonal and mostly brightly colored invertebrate which produce high biodiversity of cytolitic, neurotoxic and cardiotoxic compounds. Zoanthids containing palytoxins are reportedly among the most toxic marine organisms known. In addition, a high concentration of zoanthamine alkaloids extracted from this group.The zoanthamine alkaloids were isolated over 20 years ago, exhibit a broad range of biological activities.The best studied and most well-known biological activity of zoanthamine derivative significantly suppressed bone resorption and enhanced bone formation.

Biologically Active Macrocyclic Compounds – from Natural Products to Diversity‐Oriented Synthesis

DEFF Research Database (Denmark)

Madsen, Charlotte Marie; Clausen, Mads Hartvig

2011-01-01

Macrocyclic compounds are attractive targets when searching for molecules with biological activity. The interest in this compound class is increasing, which has led to a variety of methods for tackling the difficult macrocyclization step in their synthesis. This microreview highlights some recent...... developments in the synthesis of macrocycles, with an emphasis on chemistry developed to generate libraries of putative biologically active compounds....

Protease activated receptors (PARS) mediation in gyroxin biological activity

International Nuclear Information System (INIS)

Silva, Jose Alberto Alves da

2009-01-01

Gyroxin is a serine protease enzyme from the South American rattlesnake (Crotalus durissus terrificus) venom; it is only partially characterized and has multiple activities. Gyroxin induces blood coagulation, blood pressure decrease and a neurotoxic behavior named barrel rotation. The mechanisms involved in this neurotoxic activity are not known. Whereas gyroxin is a member of enzymes with high potential to become a new drug with clinical applications such as thrombin, batroxobin, ancrod, tripsyn and kalicrein, it is important to find out how gyroxin works. The analysis on agarose gel electrophoresis and circular dichroism confirmed the molecules' integrity and purity. The gyroxin intravenous administration in mice proved its neurotoxicity (barrel rotation). In vivo studies employing intravital microscopy proved that gyroxin induces vasodilation with the participation of protease activated receptors (PARs), nitric oxide and Na+K+ATPase. The leukocytes' adherence and rolling counting indicated that gyroxin has no pro inflammatory activity. Gyroxin induced platelet aggregation, which was blocked by inhibitors of PAR1 and PAR4 receptors (SCH 79797 and tcY-NH 2 , respectively). Finally, it was proved that the gyroxin temporarily alter the permeability of the blood brain barrier (BBB). Our study has shown that both the protease-activated receptors and nitric oxide are mediators involved in the biological activities of gyroxin. (author)

Increased Sclerostin Levels after Further Ablation of Remnant Estrogen by Aromatase Inhibitors

Directory of Open Access Journals (Sweden)

Wonjin Kim

2015-03-01

Full Text Available BackgroundSclerostin is a secreted Wnt inhibitor produced almost exclusively by osteocytes, which inhibits bone formation. Aromatase inhibitors (AIs, which reduce the conversion of steroids to estrogen, are used to treat endocrine-responsive breast cancer. As AIs lower estrogen levels, they increase bone turnover and lower bone mass. We analyzed changes in serum sclerostin levels in Korean women with breast cancer who were treated with an AI.MethodsWe included postmenopausal women with endocrine-responsive breast cancer (n=90; mean age, 57.7 years treated with an AI, and compared them to healthy premenopausal women (n=36; mean age, 28.0 years. The subjects were randomly assigned to take either 5 mg alendronate with 0.5 µg calcitriol (n=46, or placebo (n=44 for 6 months.ResultsPostmenopausal women with breast cancer had significantly higher sclerostin levels compared to those in premenopausal women (27.8±13.6 pmol/L vs. 23.1±4.8 pmol/L, P0.05.ConclusionSerum sclerostin levels increased with absolute deficiency of residual estrogens in postmenopausal women with endocrine-responsive breast cancer who underwent AI therapy with concurrent bone loss.

SYNTHESIS, REACTIVITY AND BIOLOGICAL ACTIVITY OF QUINOXALIN-2-ONE DERIVATIVES

OpenAIRE

El Mokhtar Essassi; R. Bouhfid; Y. Kandri Rodi; S. Ferfra; H. Benzeid; Y. Ramli

2010-01-01

Quinoxalines have a great interest in various fields and particularly in chemistry, biology and pharmacology. It enabled the researchers to develop many methods for their preparations and to seek new fields of application. In this review, we’ll expose different methods of synthesis of the quinoxalin-2-one, its reactivity and finally we’ll discuss the various biological activities of its derivatives.

Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

Directory of Open Access Journals (Sweden)

Nocerino N

2014-03-01

Full Text Available Nunzia Nocerino,1 Andrea Fulgione,1 Marco Iannaccone,1 Laura Tomasetta,1 Flora Ianniello,1 Francesca Martora,1 Marco Lelli,2 Norberto Roveri,2 Federico Capuano,3 Rosanna Capparelli1 1Department of Agriculture Special Biotechnology Center Federico II, CeBIOTEC Biotechnology, University of Naples Federico II, Naples, 2Department of Chemistry, G Ciamician, Alma Mater Studiorum, University of Bologna, Bologna, 3Department of Food Inspection IZS ME, Naples, Italy Abstract: The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA. We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications. Keywords: lactoferrin, hydroxyapatite nanocrystals, biomimetism, biological activity, drug delivery

Biological activity and chemical profile of Lavatera thuringiaca L. extracts obtained by different extraction approaches.

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Mašković, Pavle Z; Veličković, Vesna; Đurović, Saša; Zeković, Zoran; Radojković, Marija; Cvetanović, Aleksandra; Švarc-Gajić, Jaroslava; Mitić, Milan; Vujić, Jelena

2018-01-01

Lavatera thuringiaca L. is herbaceous perennial plant from Malvaceae family, which is known for its biological activity and richness in polyphenolic compounds. Despite this, the information regarding the biological activity and chemical profile is still insufficient. Aim of this study was to investigate biological potential and chemical profile of Lavatera thuringiaca L., as well as influence of applied extraction technique on them. Two conventional and four non-conventional extraction techniques were applied in order to obtain extracts rich in bioactive compound. Extracts were further tested for total phenolics, flavonoids, condensed tannins, gallotannins and anthocyanins contents using spectrophotometric assays. Polyphenolic profile was established using HPLC-DAD analysis. Biological activity was investigated regarding antioxidant, cytotoxic and antibacterial activities. Four antioxidant assays were applied as well as three different cell lines for cytotoxic and fifteen bacterial strain for antibacterial activity. Results showed that subcritical water extraction (SCW) dominated over the other extraction techniques, where SCW extract exhibited the highest biological activity. Study indicates that plant Lavatera thuringiaca L. may be used as a potential source of biologically compounds. Copyright © 2017 Elsevier GmbH. All rights reserved.

Toxicity of Biologically Active Peptides and Future Safety Aspects: An Update.

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Khan, Fazlullah; Niaz, Kamal; Abdollahi, Mohammad

2018-02-18

Peptides are fragments of proteins with significant biological activities. These peptides are encoded in the protein sequence. Initially, such peptides are inactive in their parental form, unless proteolytic enzymes are released. These peptides then exhibit various functions and play a therapeutic role in the body. Besides the therapeutic and physiological activities of peptides, the main purpose of this study was to highlight the safety aspects of peptides. We performed an organized search of available literature using PubMed, Google Scholar, Medline, EMBASE, Reaxys and Scopus databases. All the relevant citations including research and review articles about the toxicity of biologically active peptides were evaluated and gathered in this study. Biological peptides are widely used in the daily routine ranging from food production to the cosmetics industry and also they have a beneficial role in the treatment and prevention of different diseases. These peptides are manufactured by both chemical and biotechnological techniques, which show negligible toxicity, however, some naturally occurring peptides and enzymes may induce high toxicity. Depending upon the demand and expected use in the food or pharmaceutical industry, we need different approaches to acertain the safety of these peptides preferentially through in silico methods. Intestinal wall disruption, erythrocytes and lymphocytes toxicity, free radical production, enzymopathic and immunopathic tissue damage and cytotoxicity due to the consumption of peptides are the main problems in the biological system that lead to various complicated disorders. Therefore, before considering biologically active peptides for food production and for therapeutic purpose, it is first necessary to evaluate the immunogenicity and toxicities of peptides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

SYNTHESIS, REACTIVITY AND BIOLOGICAL ACTIVITY OF QUINOXALIN-2-ONE DERIVATIVES

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El Mokhtar Essassi

2010-04-01

Full Text Available Quinoxalines have a great interest in various fields and particularly in chemistry, biology and pharmacology. It enabled the researchers to develop many methods for their preparations and to seek new fields of application. In this review, we’ll expose different methods of synthesis of the quinoxalin-2-one, its reactivity and finally we’ll discuss the various biological activities of its derivatives.

Systems Biology Graphical Notation: Activity Flow language Level 1 Version 1.2

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Mi Huaiyu

2015-06-01

Full Text Available The Systems Biological Graphical Notation (SBGN is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD, Entity Relationship (ER and Activity Flow (AF, allow for the representation of different aspects of biological and biochemical systems at different levels of detail.

Phytotoxicity of vulpia residues: III. Biological activity of identified allelochemicals from Vulpia myuros.

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An, M; Pratley, J E; Haig, T

2001-02-01

Twenty compounds identified in vulpia (Vulpia myuros) residues as allelochemicals were individually and collectively tested for biological activity. Each exhibited characteristic allelochemical behavior toward the test plant, i.e., inhibition at high concentrations and stimulation or no effect at low concentrations, but individual activities varied. Allelopathins present in large quantities, such as syringic, vanillic, and succinic acids, possessed low activity, while those present in small quantities, such as catechol and hydrocinnamic acid, possessed strong inhibitory activity. The concept of a phytotoxic strength index was developed for quantifying the biological properties of each individual allelopathin in a concise, comprehensive, and meaningful format. The individual contribution of each allelopathin, assessed by comparing the phytotoxic strength index to the overall toxicity of vulpia residues, was variable according to structure and was influenced by its relative proportion in the residue. The majority of compounds possessed low or medium biological activity and contributed most of the vulpia phytotoxicity, while compounds with high biological activity were in the minority and only present at low concentration. Artificial mixtures of these pure allelochemicals also produced phytotoxicity. There were additive/synergistic effects evident in the properties of these mixtures. One such mixture, formulated from allelochemicals found in the same proportions as occur in vulpia extract, produced stronger activity than another formulated from the same set of compounds but in equal proportions. These results suggest that the exploration of the relative composition of a cluster of allelopathins may be more important than simply focusing on the identification of one or two compounds with strong biological activity and that synergism is fundamental to the understanding of allelopathy.

Biological activities of Rumex dentatus L: Evaluation of methanol ...

African Journals Online (AJOL)

PRECIOUS

2009-12-15

Dec 15, 2009 ... of different the extracts of R. dentatus effectively inhibited tumor ... Plants contain thousands of biologically active mole- .... The vials were kept open over night with .... between prokaryotic and eukaryotic cells (Stachel and.

[Evaluation of the total biological activity and allergenic composition of allergenic extracts].

Science.gov (United States)

Lombardero, M; González, R; Duffort, O; Juan, F; Ayuso, R; Ventas, P; Cortés, C; Carreira, J

1986-01-01

In the present study, a complete procedure is presented in order to standardize allergenic extracts, the meaning of which is the measurement of the total allergenic activity and the determination of the allergenic composition. The measurement of the biological activity comprises 2 steps: Preparation of Reference Extracts and determination of their "in vivo" activity. Evaluation of the total allergenic activity of extracts for clinical use. Reference extracts were prepared from the main allergens and their "in vivo" biological activity was determined by a quantitative skin prick test in a sample of at least 30 allergic patients. By definition, the protein concentration of Reference Extract that produces, in the allergic population, a geometric mean wheal of 75 mm.2 has an activity of 100 biological units (BUs). The determination of the biological activity of a problem extract is made by RAST inhibition. The sample is compared with the corresponding Reference Extract by this technique and, from this comparison, it is possible to quantify the activity of the problem extract in biologic units (BUs) with clinical significance. Likewise, different techniques have been used to determine the allergenic composition of extracts. These techniques comprise 2 steps: Separation of the components of the extract. Identification of the components that bind specific human IgE. The separation of the components of the extract has been carried out by isoelectric focusing (IEF) and electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE). In order to identify the allergenic components, an immunoblotting technique has been employed. The separated components in the IEF gel or SDS-PAGE gel are transferred to a nitrocellulose sheet and later on, this membrane is overlaid with a serum pool from allergic patients and a mouse monoclonal anti-human IgE, labelled with 125I. Finally, the autoradiography of the nitrocellulose membrane is obtained. In this way it is possible to compare

Generation of structurally novel short carotenoids and study of their biological activity.

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Kim, Se H; Kim, Moon S; Lee, Bun Y; Lee, Pyung C

2016-02-23

Recent research interest in phytochemicals has consistently driven the efforts in the metabolic engineering field toward microbial production of various carotenoids. In spite of systematic studies, the possibility of using C30 carotenoids as biologically functional compounds has not been explored thus far. Here, we generated 13 novel structures of C30 carotenoids and one C35 carotenoid, including acyclic, monocyclic, and bicyclic structures, through directed evolution and combinatorial biosynthesis, in Escherichia coli. Measurement of radical scavenging activity of various C30 carotenoid structures revealed that acyclic C30 carotenoids showed higher radical scavenging activity than did DL-α-tocopherol. We could assume high potential biological activity of the novel structures of C30 carotenoids as well, based on the neuronal differentiation activity observed for the monocyclic C30 carotenoid 4,4'-diapotorulene on rat bone marrow mesenchymal stem cells. Our results demonstrate that a series of structurally novel carotenoids possessing biologically beneficial properties can be synthesized in E. coli.

Reconstructing Causal Biological Networks through Active Learning.

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Hyunghoon Cho

Full Text Available Reverse-engineering of biological networks is a central problem in systems biology. The use of intervention data, such as gene knockouts or knockdowns, is typically used for teasing apart causal relationships among genes. Under time or resource constraints, one needs to carefully choose which intervention experiments to carry out. Previous approaches for selecting most informative interventions have largely been focused on discrete Bayesian networks. However, continuous Bayesian networks are of great practical interest, especially in the study of complex biological systems and their quantitative properties. In this work, we present an efficient, information-theoretic active learning algorithm for Gaussian Bayesian networks (GBNs, which serve as important models for gene regulatory networks. In addition to providing linear-algebraic insights unique to GBNs, leading to significant runtime improvements, we demonstrate the effectiveness of our method on data simulated with GBNs and the DREAM4 network inference challenge data sets. Our method generally leads to faster recovery of underlying network structure and faster convergence to final distribution of confidence scores over candidate graph structures using the full data, in comparison to random selection of intervention experiments.

Use of Aromatase Inhibitors in Large Cell Calcifying Sertoli Cell Tumors: Effects on Gynecomastia, Growth Velocity, and Bone Age

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Crocker, Melissa K.; Gourgari, Evgenia; Stratakis, Constantine A.

2014-01-01

Context: Large cell calcifying Sertoli cell tumors (LCCSCT) present in isolation or, especially in children, in association with Carney Complex (CNC) or Peutz-Jeghers Syndrome (PJS). These tumors overexpress aromatase (CYP19A1), which leads to increased conversion of delta-4-androstenedione to estrone and testosterone to estradiol. Prepubertal boys may present with growth acceleration, advanced bone age, and gynecomastia. Objective: To investigate the outcomes of aromatase inhibitor therapy (AIT) in prepubertal boys with LCCSCTs. Design: Case series of a very rare tumor and chart review of cases treated at other institutions. Setting: Tertiary care and referral center. Patients: Six boys, five with PJS and one with CNC, were referred to the National Institutes of Health for treatment of LCCSCT. All patients had gynecomastia, testicular enlargement, and advanced bone ages, and were being treated by their referring physicians with AIT. Interventions: Patients were treated for a total of 6–60 months on AIT. Main Outcome Measures: Height, breast tissue mass, and testicular size were all followed; physical examination, scrotal ultrasounds, and bone ages were obtained, and hormonal concentrations and tumor markers were measured. Results: Tumor markers were negative. All patients had decreases in breast tissue while on therapy. Height percentiles declined, and predicted adult height moved closer to midparental height as bone age advancement slowed. Testicular enlargement stabilized until entry into central puberty. Only one patient required unilateral orchiectomy. Conclusions: Patients with LCCSCT benefit from AIT with reduction and/or elimination of gynecomastia and slowing of linear growth and bone age advancement. Further study of long-term outcomes and safety monitoring are needed but these preliminary data suggest that mammoplasty and/or orchiectomy may be foregone in light of the availability of medical therapy. PMID:25226294

The time since last menstrual period is important as a clinical predictor for non-steroidal aromatase inhibitor-related arthralgia

International Nuclear Information System (INIS)

Kanematsu, Miyuki; Morimoto, Masami; Honda, Junko; Nagao, Taeko; Nakagawa, Misako; Takahashi, Masako; Tangoku, Akira; Sasa, Mitsunori

2011-01-01

The clinical predictors of aromatase inhibitor-related arthralgia (AIA), a drug-related adverse reaction of aromatase inhibitors (AIs), remain unclear. AIA was prospectively surveyed every 4 months in 328 postmenopausal breast cancer patients administered a non-steroidal AI (anastrozole). Various clinicopathological parameters were recorded and analyzed (chi-square test, Fisher's exact test and logistic regression analysis). The mean observation period was 39.9 months. AIA manifested in 114 patients (34.8%), with peaks of onset at 4 (33.7%) and 8 months (11.4%) after starting AI administration. Some cases manifested even after 13 months. AIA tended to occur in younger patients (incidences of 46.3%, 37.4% and 28.0% for ages of < 55, 55-65 and > 65 years, respectively (p = 0.063)) and decreased significantly with the age at menarche (53.3%, 35.3% and 15.4% for < 12, 12-15 and > 15 years, respectively (p = 0.036)). The incidences were 45.1%, 46.3 and 25.1% for the time since the last menstrual period (LMP) < 5 years, 5-10 years and > 10 years, being significantly lower at > 10 years (p < 0.001). In logistic regression analysis, the AIA incidence was significantly lower in the time since LMP > 10-year group versus the < 5-year group (odds ratio 0.44, p = 0.002), but the age at menarche showed no association. AIA manifested significantly earlier (≤ 6 months) as the time since LMP became shorter (< 5 years). AIA tends to manifest early after starting AI, but some cases show delayed onset. The incidence was significantly lower in patients with a duration of > 10 years since LMP. When the time since LMP was short, the onset of AIA was significantly earlier after starting AI administration

Synthetic Approaches and Biological Activities of 4-Hydroxycoumarin Derivatives

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Oee-Sook Park

2009-11-01

Full Text Available The main purpose of this review is to summarize recent chemical syntheses and structural modifications of 4-hydroxycoumarin and its derivatives, of interest due to their characteristic conjugated molecular architecture and biological activities.

Spectroscopic study of biologically active glasses

Science.gov (United States)

Szumera, M.; Wacławska, I.; Mozgawa, W.; Sitarz, M.

2005-06-01

It is known that the chemical activity phenomenon is characteristic for some inorganic glasses and they are able to participate in biological processes of living organisms (plants, animals and human bodies). An example here is the selective removal of silicate-phosphate glass components under the influence of biological solutions, which has been applied in designing glasses acting as ecological fertilizers of controlled release rate of the nutrients for plants. The structure of model silicate-phosphate glasses containing the different amounts of the glass network formers, i.e. Ca 2+ and Mg 2+, as a binding components were studied. These elements besides other are indispensable of the normal growth of plants. In order to establish the function and position occupied by the particular components in the glass structure, the glasses were examined by FTIR spectroscopy (with spectra decomposition) and XRD methods. It has been found that the increasing amount of MgO in the structure of silicate-phosphate glasses causes the formation of domains the structure of which changes systematically from a structure of the cristobalite type to a structure corresponding to forsterite type. Whilst the increasing content of CaO in the structure of silicate-phosphate glasses causes the formation of domains the structure of which changes from a structure typical for cristobalite through one similar to the structure of calcium orthophosphate, to a structure corresponding to calcium silicates. The changing character of domains structure is the reason of different chemical activity of glasses.

Recent Advances in Momordica charantia: Functional Components and Biological Activities

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Shuo Jia

2017-11-01

Full Text Available Momordica charantia L. (M. charantia, a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia.

Recent Advances in Momordica charantia: Functional Components and Biological Activities.

Science.gov (United States)

Jia, Shuo; Shen, Mingyue; Zhang, Fan; Xie, Jianhua

2017-11-28

Momordica charantia L. ( M. charantia ), a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia .

Biologically Active Metabolites Synthesized by Microalgae

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Michele Greque de Morais

2015-01-01

Full Text Available Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences.

The importance of extremophile cyanobacteria in the production of biologically active compounds

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Drobac-Čik Aleksandra V.

2007-01-01

Full Text Available Due to their ability to endure extreme conditions, terrestrial cyanobacteria belong to a group of organisms known as "extremophiles". Research so far has shown that these organisms posses a great capacity for producing biologically active compounds (BAC. The antibacterial and antifungal activities of methanol extracts of 21 cyanobacterial strains belonging to Anabaena and Nostoc genera, previously isolated from different soil types and water resources in Serbia, were evaluated. In general, larger number of cyanobacterial strains showed antifungal activity. In contrast to Nostoc, Anabaena strains showed greater diversity of antibacterial activity (mean value of percentages of sensitive targeted bacterial strains 3% and 25.9% respectively. Larger number of targeted fungi was sensitive to cultural liquid extract (CL, while crude cell extract (CE affected more bacterial strains. According to this investigation, the higher biological activity of terrestrial strains as representatives of extremophiles may present them as significant BAC producers. This kind of investigation creates very general view of cyanobacterial possibility to produce biologically active compounds but it points out the necessity of exploring terrestrial cyanobacterial extremophiles as potentially excellent sources of these substances and reveals the most prospective strains for further investigations.

Designing and testing a classroom curriculum to teach preschoolers about the biology of physical activity: The respiration system as an underlying biological causal mechanism

Science.gov (United States)

Ewing, Tracy S.

The present study examined young children's understanding of respiration and oxygen as a source of vital energy underlying physical activity. Specifically, the purpose of the study was to explore whether a coherent biological theory, characterized by an understanding that bodily parts (heart and lungs) and processes (oxygen in respiration) as part of a biological system, can be taught as a foundational concept to reason about physical activity. The effects of a biology-based intervention curriculum designed to teach preschool children about bodily functions as a part of the respiratory system, the role of oxygen as a vital substance and how physical activity acts an energy source were examined. Participants were recruited from three private preschool classrooms (two treatment; 1 control) in Southern California and included a total of 48 four-year-old children (30 treatment; 18 control). Findings from this study suggested that young children could be taught relevant biological concepts about the role of oxygen in respiratory processes. Children who received biology-based intervention curriculum made significant gains in their understanding of the biology of respiration, identification of physical and sedentary activities. In addition these children demonstrated that coherence of conceptual knowledge was correlated with improved accuracy at activity identification and reasoning about the inner workings of the body contributing to endurance. Findings from this study provided evidence to support the benefits of providing age appropriate but complex coherent biological instruction to children in early childhood settings.

Association of aromatase (TTTA)n repeat polymorphisms with central precocious puberty in girls.

Science.gov (United States)

Lee, Hae Sang; Kim, Kyung Hee; Hwang, Jin Soon

2014-09-01

Precocious puberty is characterized by early activation of the pituitary-gonadal axis. Oestrogen is the final key factor to start the onset of puberty. The cytochrome P450 19A1 (CYP19A1) gene encodes an aromatase that is responsible for the conversion of androgens to oestrogen, which is a key step in oestrogen biosynthesis. The aim of this study was to identify CYP19A1 gene mutations or polymorphisms in girls with central precocious puberty (CPP). We evaluated the frequency of allelic variants of the CYP19A1 exons and the tetranucleotide tandem repeat (TTTA)n in intron 4 in 203 idiopathic central precocious puberty (CPP) girls and 101 normal healthy women. The genotype analysis of the CYP19A1 (TTTA)n polymorphism revealed six different alleles ranging from seven to 13 repeats. Among the six different repeat alleles detected in this study, the (TTTA)₁₃ repeat allele was only detected in the patient group and carriers of the (TTTA)₁₃ allele were significantly associated with an increased risk of CPP (OR = 1·509, 95% CI = 1·425-1·598, P = 0·033). Carriers of the (TTTA)₁₃ repeat allele were significantly younger at pubertal onset and had higher levels of oestrogen than noncarriers of the (TTTA)₁₃ repeat allele. Although nine polymorphisms were detected in exons of the CYP19A1 gene, no clinical significance was observed. In this study, carriers of a higher repeat (TTTA)₁₃ polymorphism in intron 4 of the CYP19A1 gene had higher levels of oestrogen. Those carrying the (TTTA)₁₃ repeat allele may have a higher risk of developing CPP. © 2014 John Wiley & Sons Ltd.

Radiation degradation of carbohydrates and their biological activities for plants

International Nuclear Information System (INIS)

Kume, T.; Nagasawa, N.; Matsuhashi, S.

2000-01-01

Radiation effects on carbohydrates such as chitosan, sodium alginate, carrageenan, cellulose, pectin have been investigated to improve the biological activities. These carbohydrates were easily degraded by irradiation and induced various kinds of biological activities such as anti-bacterial activity, promotion of plant growth, suppression of heavy metal stress, phytoalexins induction. Pectic fragments obtained from degraded pectin induced the phytoalexins such as glyceollins in soybean and pisatin in pea. The irradiated chitosan shows the higher elicitor activity for pisatin than that of pectin. For the plant growth promotion, alginate derived from brown marine algae, chitosan and ligno-cellulosic extracts show a strong activity. Kappa and iota carrageenan derived from red marine algae can promote growth of rice and the highest effect was obtained with kappa irradiated at 100 kGy. Some radiation degraded carbohydrates suppressed the damage of heavy metals on plants. The effects of irradiated carbohydrates on transportation of heavy metals have been investigated by PETIS (Positron Emitting Tracer Imaging System) and autoradiography using 48 V and 62 Zn. (author)

Suitable activated stable nuclide tracer technique and its applications in biology and medicine

International Nuclear Information System (INIS)

Zhang Weicheng

1989-01-01

Stable isotopes as tracers in biology and medicine have been more extensively used. Mass spectrometry has been a classic technique in the analysis of stable isotopes because it is very sensitive and precise. Activation analysis has recently been introduced as an analytical tool. Its fast speed and simplicity is a great advantage for handling large batches of samples in isotopic tracer experiments. The combination of enriched stable isotope tracer studies and activation analysis techniques has become an ideal and reliable technique, especially in the fields of biology and medicine. This paper presents a survey of the fundamental principle, the character and the applications in biology and medicine for the suitable activated stable isotope tracer techniques

Biological activity of phenolic compounds present in buckwheat plants

Czech Academy of Sciences Publication Activity Database

Kalinová, J.; Tříska, Jan; Vrchotová, Naděžda

2005-01-01

Roč. 16, č. 1 (2005), s. 123-129 ISSN 0971-4693 Institutional research plan: CEZ:AV0Z60870520 Keywords : biological activity, extract, Fagopyrum esculenthum Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.686, year: 2005

Biologically active polymers from spontaneous carotenoid oxidation: a new frontier in carotenoid activity.

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James B Johnston

Full Text Available In animals carotenoids show biological activity unrelated to vitamin A that has been considered to arise directly from the behavior of the parent compound, particularly as an antioxidant. However, the very property that confers antioxidant activity on some carotenoids in plants also confers susceptibility to oxidative transformation. As an alternative, it has been suggested that carotenoid oxidative breakdown or metabolic products could be the actual agents of activity in animals. However, an important and neglected aspect of the behavior of the highly unsaturated carotenoids is their potential to undergo addition of oxygen to form copolymers. Recently we reported that spontaneous oxidation of ß-carotene transforms it into a product dominated by ß-carotene-oxygen copolymers. We now report that the polymeric product is biologically active. Results suggest an overall ability to prime innate immune function to more rapidly respond to subsequent microbial challenges. An underlying structural resemblance to sporopollenin, found in the outer shell of spores and pollen, may allow the polymer to modulate innate immune responses through interactions with the pattern recognition receptor system. Oxygen copolymer formation appears common to all carotenoids, is anticipated to be widespread, and the products may contribute to the health benefits of carotenoid-rich fruits and vegetables.

Determination of biologically active phenols and polyphenols in various objects by chromatographic techniques

International Nuclear Information System (INIS)

Kochetova, M V; Semenistaya, E N; Larionov, Oleg G; Revina, A A

2007-01-01

Chromatographic techniques for determination of biologically active phenols and polyphenols are considered. Various methods for sample preparation and detection are compared. The advantages of high performance liquid chromatography with spectrophotometric detection for determination of antioxidants are demonstrated. Data on determination of biologically active phenols and polyphenols published in the period from 1995 to 2005 are analysed.

Charged particle activation analysis of phosphorus in biological materials

International Nuclear Information System (INIS)

Masumoto, K.; Yagi, M.

1983-01-01

Charged particle activation analysis of phosphorus in biological materials using the 31 P(α,n) sup(34m)Cl reaction has been studied. Since sup(34m)Cl is also produced by the 32 S(α,pn) and the 35 Cl(α,α'n) reactions, the thick-target yield curves on phosphorus, sulfur and chlorine were determined in order to choose the optimum irradiation conditions. As a result, it was found that the activation analysis for phosphorus without interferences from sulfur and chlorine is possible by bombarding with less than 17 MeV alphas. The applicability of this method to biological samples was then examined by irradiating several standard reference materials. It was confirmed that phosphorus can readily be determined at the detection limit of 1μg free from interferences due to the matrix elements. (author)

Biological activities and medicinal properties of Cajanus cajan (L Millsp.

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Dilipkumar Pal

2011-01-01

Full Text Available Cajanus cajan (L Millsp. (Sanskrit: Adhaki, Hindi: Arhar, English: Pigeon pea, Bengali: Tur (family: Fabaceae is the most important grain legume crop of rain-fed agriculture in semi-arid tropics. It is both a food crop and a cover/forage crop with high levels of proteins and important amino acids like methionine, lysine and tryptophan. During the last few decades extensive studies have been carried out regarding the chemistry of C. cajan and considerable progress has been achieved regarding its biological activities and medicinal applications. This review article gives an overview on the biological activities of the compounds isolated, pharmacological actions and clinical studies of C. cajan extracts apart from its general details.

Biological activities and medicinal properties of Cajanus cajan (L) Millsp.

Science.gov (United States)

Pal, Dilipkumar; Mishra, Pragya; Sachan, Neetu; Ghosh, Ashoke K

2011-10-01

Cajanus cajan (L) Millsp. (Sanskrit: Adhaki, Hindi: Arhar, English: Pigeon pea, Bengali: Tur) (family: Fabaceae) is the most important grain legume crop of rain-fed agriculture in semi-arid tropics. It is both a food crop and a cover/forage crop with high levels of proteins and important amino acids like methionine, lysine and tryptophan. During the last few decades extensive studies have been carried out regarding the chemistry of C. cajan and considerable progress has been achieved regarding its biological activities and medicinal applications. This review article gives an overview on the biological activities of the compounds isolated, pharmacological actions and clinical studies of C. cajan extracts apart from its general details.

Activating and inhibiting connections in biological network dynamics

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Knight Rob

2008-12-01

Full Text Available Abstract Background Many studies of biochemical networks have analyzed network topology. Such work has suggested that specific types of network wiring may increase network robustness and therefore confer a selective advantage. However, knowledge of network topology does not allow one to predict network dynamical behavior – for example, whether deleting a protein from a signaling network would maintain the network's dynamical behavior, or induce oscillations or chaos. Results Here we report that the balance between activating and inhibiting connections is important in determining whether network dynamics reach steady state or oscillate. We use a simple dynamical model of a network of interacting genes or proteins. Using the model, we study random networks, networks selected for robust dynamics, and examples of biological network topologies. The fraction of activating connections influences whether the network dynamics reach steady state or oscillate. Conclusion The activating fraction may predispose a network to oscillate or reach steady state, and neutral evolution or selection of this parameter may affect the behavior of biological networks. This principle may unify the dynamics of a wide range of cellular networks. Reviewers Reviewed by Sergei Maslov, Eugene Koonin, and Yu (Brandon Xia (nominated by Mark Gerstein. For the full reviews, please go to the Reviewers' comments section.

Cardiovascular Disease After Aromatase Inhibitor Use.

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Haque, Reina; Shi, Jiaxiao; Schottinger, Joanne E; Chung, Joanie; Avila, Chantal; Amundsen, Britta; Xu, Xiaoqing; Barac, Ana; Chlebowski, Rowan T

2016-12-01

Cardiovascular disease (CVD) is an important cause of death in older patients with breast cancer. However, limited information exists on the long-term effect of aromatase inhibitor (AI) use on CVD risk in breast cancer survivors. To this point, no other population-based studies have been able to adjust for CVD risk factors or cardiovascular medications. To determine the long-term influence of adjuvant endocrine therapies on CVD in a cohort of postmenopausal breast cancer survivors in analyses that accounted for major CVD risk factors, medication use, chemotherapy, and radiotherapy. A retrospective cohort of postmenopausal women with breast cancer diagnosed from January 1, 1991, to December 31, 2010, and followed up through December 31, 2011 (maximum, 21 years [72 886 person-years]), was evaluated using records from a managed care organization with nearly 20 community hospitals in California. A total of 13 273 postmenopausal women with hormone receptor-positive breast cancer without prior CVD were included. Cardiovascular disease incidence was compared across endocrine therapy categories. Information on demographics, comorbidity, medication, use, and CVD risk was captured from electronic health records. Multivariate Cox proportional hazards models using time-dependent endocrine drug use variables and propensity scores were conducted. Data analysis was conducted from September 15, 2014, to February 1, 2016. Women were grouped by endocrine therapy status (tamoxifen citrate only, AI only, both, or neither). Person-year rates of CVD for each therapy group. During 72 886 person-years in 13 273 women (mean [SD] age, 66.8 [8.1] years) with follow-up through 2011, we observed 3711 CVD events. In multivariable analyses (reported as hazard ratio [95% CI]), AI-only users had a similar risk of cardiac ischemia (myocardial infarction and angina) (adjusted, 0.97 [0.78-1.22]) and stroke (adjusted, 0.97 [0.70-1.33]) as tamoxifen-only users (reference). However, we found an

Aktivitas Biologis Imunoglobulin Yolk Anti Parvovirus Setelah Perlakuan Suhu (BIOLOGY ACTIVITIES OF IgY PARVOVIRUS AFTER HEAT TREATMENT

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I Gusti Ayu Agung Suartini

2016-02-01

Full Text Available This study aims to determine the effect of temperature on the biological activity of various crude and precipitate specific Immunoglobulin (IgY Canine parvovirus (CPV. Hiperimun serum conducted on Isa Brown chickens injected with antigen CPV. Crude yolk Ig preparations derived from chicken serum without purification while the yolk Ig preparations precipitates obtained by the chicken serum was precipitated with ammonium sulfate and dialyzed. Both types of Ig yolk given treatment temperature 50ºC, 60ºC, 70ºC, and 80ºC for 15 minutes. To test Gel Precipitation Test (AGPT is performed to determine whether there is a specific IgY CPV in the serum of chickens. Biological activity of both types of Ig detected with Barriers Haemagglutination test (HI. The design used in this study is completely randomized design factorial. The results of this study indicate that the temperature was highly significant on the activities of IgY crude and precipitates. Activities IgY crude and precipitate down to the treatment temperature of 50ºC, 60ºC, 70ºC, and 80ºC. Geometric Mean Titer crude IgY respectively - were 26.67, 26, 25.33, and <2º Unit HI while IgY precipitates are respectively 26.33, 25.67, 24, and <2º Unit HI. Based on the results of this study concluded that the biological activity of crude IgY better than IgY precipitates after treatment of a wide range of temperatures.

An insight into the biological activities of heterocyclic-fatty acid hybrid molecules.

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Venepally, Vijayendar; Reddy Jala, Ram Chandra

2017-12-01

Heterocyclic compounds are the interesting core structures for the development of new bioactive compounds. Fatty acids are derived from renewable raw materials and exhibit various biological activities. Several researchers are amalgamating these two bioactive components to yield bioactive hybrid molecules with some desirable features. Heterocyclic-fatty acid hybrid derivatives are a new class of heterocyclic compounds with a broad range of biological activities and significance in the field of medicinal chemistry. Over the last few years, many research articles emphasized the significance of heterocyclic-fatty acid hybrid derivatives. The present review article focuses the developments in designing and biological evaluation of heterocyclic-fatty acid hybrid molecules. Copyright © 2017. Published by Elsevier Masson SAS.

Diversity of Secondary Metabolites from Marine Bacillus Species: Chemistry and Biological Activity

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Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Islam, Mohammad Tofazzal

2013-01-01

Marine Bacillus species produce versatile secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, and isocoumarins. These structurally diverse compounds exhibit a wide range of biological activities, such as antimicrobial, anticancer, and antialgal activities. Some marine Bacillus strains can detoxify heavy metals through reduction processes and have the ability to produce carotenoids. The present article reviews the chemistry and biological activities of secondary metabolites from marine isolates. Side by side, the potential for application of these novel natural products from marine Bacillus strains as drugs, pesticides, carotenoids, and tools for the bioremediation of heavy metal toxicity are also discussed. PMID:23941823

Spectral parameters and biological activity of macromolecular compounds of humic etiology

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M. V. Zykova

2017-01-01

Full Text Available Materials and methods. 18 native humic acids (HAs were received from nine representative types of peat of the Tomsk region. Two extraction methods were used: sodium hydroxide and sodium pyrophosphate. Molecular structure parameters were investigated by IR-spectroscopy. The assessement of qualitative and quantitative features of the IR-spectra of 18 different humic acids was made. When HAs with mouse macrophages were cultured their ability to influence the NO-stimulation was determined. Thus, the biological activity of HAs and its dependence on the parameters of the molecular structure were studied.Results. The results of infrared spectroscopy showed that the HAs of upland types of peat contain more carbonyl, carboxyl, and ester groups, and HAs of lowland types of peat contain more aromatic carbon, phenolic and alcoholic hydroxyl, ether and carbohydrate fragments. The results of biological activity showed that HAs from upland types of peat induce the formation of nitrogen oxide, wherein the cell activation decreases with HAs obtained by alkali. All types of HAs from lowland types of peat contain an admixture of endotoxin. Some HAs obtained by sodium pyrophosphate have higher immunotropic activity; the HAs can cause antigen-specific stimulation of cells. The activity of HAs does not depend on endotoxin admixture. The results of molecular spectroscopy showed that the most biologically active HAs have higher aromaticity and higher concentration of oxygen-containing functional groups. This result can be used as a marker factor in the standardization of HAs. 

Implications of the use of experimental activities in biology education in public schools

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Vânia Cardoso da Silva Morais

2016-04-01

Full Text Available This study aimed to verify the influence of a didactic sequence with experimental activities on student motivation in relation to the subject matter Biology and check the possibility of applying such a result having as input the cultural-historical perspective and the dynamic of the three pedagogical moments. The work is part of a Master Degree research developed with 70 students from a high school in Patos de Minas city. The analysis of the data collected through observation, questionnaires, reports, testimonies of students, filming and photography of biology classes, points out that the use of experimental activities in Biology classes contributed to the increase of student motivation relating to Biology classes favoring the teaching-learning process and also to promote a converge between the scientific knowledge and reality of the students besides encourage their self-esteem and investigative sense. The results also indicate that it is possible to develop at school a didactic sequence based on the complementarity of two different theoretical lines like the dynamics of the three moments and in the historical and cultural perspective. Based on above considerations, we believe that the use of experimental activities following didactics positively influences student motivation in relation to Biology, favoring the teaching and learning of Biology. However, it is the whole of this, as the theory and the posture of motivating teachers, allowed approximation between scientific knowledge and reality of the students, enabling greater learning of biological concepts.

Effects of in ovo exposure of Imazalil and Atrazine on sexual differentiation in chick gonads

Energy Technology Data Exchange (ETDEWEB)

Yamashita, J.; Ikeda, M. [Univ. of Shizuoka, Shizuoka (Japan); Matsushita, S.; Iwasawa, T.; Ikeya, M. [Shizuoka Swine and Poultry Experiment Station, Kikugawa (Japan)

2004-09-15

numerous anti-fungal chemicals. These chemicals have shown to reversibly (although not necessarily competitively) inhibit aromatase activity in human placental microsomes. It is reported that imazalil and difenoconazole inhibit aromatase activity in human adrenocortical carcinoma cell line H295R. Atrazine is the most commonly used herbicide in the word. There are several reports about the adverse effects of atrazine exposure. Atrazine induced hermaphroditism in African clawed frogs and demasculinized the larynx in male frogs. Plasma testosterone concentration in male frogs was decreased by atrazine exposure, and plasma estradiol concentration in rats was increased by atrazine exposure. Atrazine also increased aromatase activity in human adrenocortical carcinoma cell line H295R by inducing aromatase mRNA. In this study, the effects of in ovo exposure to an aromatase-inhibiting chemical (imazalil) and an aromatase-activating chemical (atrazine) on the sexual differentiation of chick gonad were investigated.

Biological treatment of textile mill wastewater in the. presence of activated carbon

International Nuclear Information System (INIS)

Liaquat, F.; Hassan, M.; Mahboob, S.; Rehman, A.; Liaquat, S.; Khalid, Z.M.

2005-01-01

The main goal of this study was to find out effectiveness of biological treatment for the reduction in chemical oxygen demand (COD) and biological oxygen demand (BOD) of the textile processing industrial wastewater in the absence and presence of granular activated carbon (GAC) in shake flask experiment. To check the pollution level, physio-chemical analysis of effluent from Amtex industry (Faisalabad) was carried out. The outlet effluent contained high value of COD (1100 mg/l), BOD (309 mg/l) with pH 9.2, electrical conductivity (Ec) 3.7 mS/m, total dissolved solids (TDS) (2640 mg/l), total solids (TS) (3060 mg/l), total suspended solids (TSS) (420 19/l) and phenol (.34 mg/l). After initial period of activated sludge adaptation to wastewater, shake flask batch cultures (with and without activated carbon) were operated on lab scale. The COD and BOD were noted after very 12 hours for 3 days. The maximum reduction in COD (82%) and BOD (90%) was observed biological treatment in presence of activated carbon at retention time of 72 hours. (author)

Astaxanthin: Sources, Extraction, Stability, Biological Activities and Its Commercial Applications—A Review

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Ranga Rao Ambati

2014-01-01

Full Text Available There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3′-dihydroxy-β, β′-carotene-4,4′-dione is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum, and Phaffia rhodozyma. It accumulates up to 3.8% on the dry weight basis in H. pluvialis. Our recent published data on astaxanthin extraction, analysis, stability studies, and its biological activities results were added to this review paper. Based on our results and current literature, astaxanthin showed potential biological activity in in vitro and in vivo models. These studies emphasize the influence of astaxanthin and its beneficial effects on the metabolism in animals and humans. Bioavailability of astaxanthin in animals was enhanced after feeding Haematococcus biomass as a source of astaxanthin. Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization. Astaxanthin products are used for commercial applications in the dosage forms as tablets, capsules, syrups, oils, soft gels, creams, biomass and granulated powders. Astaxanthin patent applications are available in food, feed and nutraceutical applications. The current review provides up-to-date information on astaxanthin sources, extraction, analysis, stability, biological activities, health benefits and special attention paid to its commercial applications.

Refolding techniques for recovering biologically active recombinant proteins from inclusion bodies.

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Yamaguchi, Hiroshi; Miyazaki, Masaya

2014-02-20

Biologically active proteins are useful for studying the biological functions of genes and for the development of therapeutic drugs and biomaterials in a biotechnology industry. Overexpression of recombinant proteins in bacteria, such as Escherichia coli, often results in the formation of inclusion bodies, which are protein aggregates with non-native conformations. As inclusion bodies contain relatively pure and intact proteins, protein refolding is an important process to obtain active recombinant proteins from inclusion bodies. However, conventional refolding methods, such as dialysis and dilution, are time consuming and, often, recovered yields of active proteins are low, and a trial-and-error process is required to achieve success. Recently, several approaches have been reported to refold these aggregated proteins into an active form. The strategies largely aim at reducing protein aggregation during the refolding procedure. This review focuses on protein refolding techniques using chemical additives and laminar flow in microfluidic chips for the efficient recovery of active proteins from inclusion bodies.

Refolding Techniques for Recovering Biologically Active Recombinant Proteins from Inclusion Bodies

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Hiroshi Yamaguchi

2014-02-01

Full Text Available Biologically active proteins are useful for studying the biological functions of genes and for the development of therapeutic drugs and biomaterials in a biotechnology industry. Overexpression of recombinant proteins in bacteria, such as Escherichia coli, often results in the formation of inclusion bodies, which are protein aggregates with non-native conformations. As inclusion bodies contain relatively pure and intact proteins, protein refolding is an important process to obtain active recombinant proteins from inclusion bodies. However, conventional refolding methods, such as dialysis and dilution, are time consuming and, often, recovered yields of active proteins are low, and a trial-and-error process is required to achieve success. Recently, several approaches have been reported to refold these aggregated proteins into an active form. The strategies largely aim at reducing protein aggregation during the refolding procedure. This review focuses on protein refolding techniques using chemical additives and laminar flow in microfluidic chips for the efficient recovery of active proteins from inclusion bodies.

Using Active Learning in a Studio Classroom to Teach Molecular Biology

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Nogaj, Luiza A.

2013-01-01

This article describes the conversion of a lecture-based molecular biology course into an active learning environment in a studio classroom. Specific assignments and activities are provided as examples. The goal of these activities is to involve students in collaborative learning, teach them how to participate in the learning process, and give…

Tests of biological activity of metabolites from Penicillium expansum (Link Thom various isolates

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Halina Borecka

2013-12-01

Full Text Available Aqrobacterium tumefaciens and cucumber, mustard and linseeds were compared as test organisms for evaluation of the biological activity of patulin. It was found that the reaction of cucumber seeds and linseed to the patulin concentrations was more pronounced than that of mustard and Aqrobacterium tumefaciens. The activity of metabolites produced by Penicillium expansum was investigated with the use of cucumber seeds. As measure of activity served the percentage of radicule growth inhibition was compared with the growth in control seeds. The biological activity of the metabolites was specific for the isolates, those from apples being more active. Thirty two isolates from pears and 34 from apples were examined.

Manipulation of broiler chickens sex differentiation by in ovo injection of aromatase inhibitors, and garlic and tomato extracts.

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Fazli, Nahid; Hassanabadi, Ahmad; Mottaghitalab, Majid; Hajati, Hosna

2015-11-01

The influence of in ovo administration of aromatase inhibitors, clomiphen citrate, tomoxifen, and garlic and tomato extracts on sex differentiation in broiler chickens were investigated in 2 experiments. Five hundred, and 1,000 fertile eggs from Ross 308 strain were used in experiments 1 and 2, respectively. In both experiments, eggs were divided into 5 groups: control group (DW, 0.1 mL/egg), tomoxifen (0.05 mg/egg), clomiphene citrate (0.05 mg/egg), garlic and tomato extracts (0.1 mL/egg). Eggs were sanitized and prepared for incubation in a regular automatic hatchery. Experimental preparations were injected into eggs at day 5 of the incubation period. Injection sites on the eggs were cleaned with 70% ethylic alcohol, bored by a needle, and aromatase inhibitors were injected into the white from the thin end of the eggs by insulin syringe and then sealed by melted paraffin. In experiment 1, hatched one-day-old chicks (mixed-sex) were raised till 42 days of age in 25 floor pens with a completely randomized design. Experiment 2 was designed to investigate the effects of sex and treatments on the feed-to-gain ratio of broiler chicks. In experiment 2, hatched one-day-old chicks were feather sexed and raised till 42 days of age in 50 floor pens. A completely randomized design with a 2 × 5 factorial arrangement of treatments (sex×treatment) was used. Gonads of the chicks were checked to determine their sex on day 42 by optic microscope to make sure feather sexing was correct. At the end of both experiments, on day 42, one bird from each pen was slaughtered for carcass analysis. In experiment 1, hatchability and the one-day-old weight of chicks showed no significant differences among treatments (P > 0.05). However, in ovo administration of garlic and tomato extracts caused the highest percentage of male chicks (P 0.05). © 2015 Poultry Science Association Inc.

European activities in space radiation biology and exobiology

International Nuclear Information System (INIS)

Horneck, G.

1996-01-01

In view of the space station era, the European Space Agency has initiated a review and planning document for space life sciences. Radiation biology includes dosimetry of the radiation field and its modification by mass shielding, studies on the biological responses to radiation in space, on the potential impact of space flight environment on radiation effects, and assessing the radiation risks and establishing radiation protection guidelines. To reach a better understanding of the processes leading to the origin, evolution and distribution of life, exobiological activities include the exploration of the solar system, the collection and analysis of extraterrestrial samples and the utilization of space as a tool for testing the impact of space environment on organics and resistant life forms. (author)

Radio-active waste disposal and deep-sea biology

International Nuclear Information System (INIS)

Rice, A.L.

1978-01-01

The deep-sea has been widely thought of as a remote, sparsely populated, and biologically inactive environment, well suited to receive the noxious products of nuclear fission processes. Much of what is known of abyssal biology tends to support this view, but there are a few disquieting contra-indications. The realisation, in recent years, that many animal groups show a previously unsuspected high species diversity in the deep-sea emphasized the paucity of our knowledge of this environment. More dramatically, the discovery of a large, active, and highly mobile abysso-bentho-pelagic fauna changed the whole concept of abyssal life. Finally, while there is little evidence for the existence of vertical migration patterns linking the deep-sea bottom communities with those of the overlying water layers, there are similarly too few negative results for the possibility of such transport mechanisms to be dismissed. In summary, biological knowledge of the abyss is insufficient to answer the questions raised in connection with deep-sea dumping, but in the absence of adequate answers it might be dangerous to ignore the questions

Biological Activities and Phytochemicals of Swietenia macrophylla King

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Habsah Abdul Kadir

2013-08-01

Full Text Available Swietenia macrophylla King (Meliaceae is an endangered and medicinally important plant indigenous to tropical and subtropical regions of the World. S. macrophylla has been widely used in folk medicine to treat various diseases. The review reveals that limonoids and its derivatives are the major constituents of S. macrophylla. There are several data in the literature indicating a great variety of pharmacological activities of S. macrophylla, which exhibits antimicrobial, anti-inflammatory, antioxidant effects, antimutagenic, anticancer, antitumor and antidiabetic activities. Various other activities like anti-nociceptive, hypolipidemic, antidiarrhoeal, anti-infective, antiviral, antimalarial, acaricidal, antifeedant and heavy metal phytoremediation activity have also been reported. In view of the immense medicinal importance of S. macrophylla, this review aimed at compiling all currently available information on its ethnomedicinal uses, phytochemistry and biological activities of S. macrophylla, showing its importance.

Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery.

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Simm, Jaak; Klambauer, Günter; Arany, Adam; Steijaert, Marvin; Wegner, Jörg Kurt; Gustin, Emmanuel; Chupakhin, Vladimir; Chong, Yolanda T; Vialard, Jorge; Buijnsters, Peter; Velter, Ingrid; Vapirev, Alexander; Singh, Shantanu; Carpenter, Anne E; Wuyts, Roel; Hochreiter, Sepp; Moreau, Yves; Ceulemans, Hugo

2018-05-17

In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, whole organisms, or expensive or rare reagents. We hypothesized that data from a single high-throughput imaging assay can be repurposed to predict the biological activity of compounds in other assays, even those targeting alternate pathways or biological processes. Indeed, quantitative information extracted from a three-channel microscopy-based screen for glucocorticoid receptor translocation was able to predict assay-specific biological activity in two ongoing drug discovery projects. In these projects, repurposing increased hit rates by 50- to 250-fold over that of the initial project assays while increasing the chemical structure diversity of the hits. Our results suggest that data from high-content screens are a rich source of information that can be used to predict and replace customized biological assays. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biological activities (anti-inflammatory and anti-oxidant) of fractions ...

African Journals Online (AJOL)

Biological activities (anti-inflammatory and anti-oxidant) of fractions and methanolic extract of Philonotis hastate (Duby Wijk & MargaDant). ... The fractions and methanolic extract exhibited moderate antioxidant potentials with various models. The flavonoid contents of the methanol extract and fractions ranged between 1.70 ...

Proximate composition, phytochemical screening, GC-MS studies of biologically active cannabinoids and antimicrobial activities of Cannabis indica

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Muhammad Saqib Isahq

2015-11-01

Full Text Available Objective: To investigate the proximate composition, minerals analysis, phytochemical screening, gas chromatography-mass spectrometry (GC-MS studies of active cannabinoids and antimicrobial activities of Cannabis indica (C. indica leaves, stems, and seeds. Methods: Standard qualitative protocols of phytochemical screening were accomplished for the identification of biologically active phytochemicals. Minerals in plant samples were analyzed by using atomic absorption spectrophotometer. The resins of C. indica were analyzed for medicinally active cannabinoid compounds by GC-MS. The sample for GC-MS study was mixed with small quantity of n-hexane and 30 mL of acetonitrile solution for the identification of cannabinoids. Agar well diffusion method was used for antibacterial activity. For antifungal activity, the tested fungal strains were sub-cultured on Sabouraud’s dextrose agar at 28 °C. Results: Mineral analysis revealed the presence of sodium, potassium, magnesium and some other minerals in all parts of C. indica. Phytochemical investigation showed the presence of alkaloids, saponins, tannins, flavonoids, sterols and terpenoids. C. indica divulged wide spectrum of antibacterial activities against Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, and Proteus mirabilis. The extracts of plant leaves, seeds and stems showed significant antifungal activities against Aspergillus niger, Aspergillus parasiticus, and Aspergillus oryzae. The biologically active cannabinoids of delta-9-tetrahydrocannabinol (25.040% and cannabidiol (resorcinol, 2-p-mentha-1,8-dien-4-yl-5-pentyl (50.077% were found in Cannabis resin in high percentage. Conclusions: The findings of the study suggested that the existence of biologically active remedial cannabinoids in elevated concentrations and antimicrobial bioassays of C. indica make it a treasured source to be used in herbal preparation for various ailments.

Effects of heat on the biological activity of wild Cordyceps sinensis

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Pengkai Wu

2015-01-01

Conclusions: These results suggested that heat treatment does not adversely affect SOD or DNase activity, polysaccharide content, or cordycepin dissolution. Thus, heat treatment might be a safe processing method to extend the storage time of wild C. sinensis without compromising biological activity.

In vitro gamma irradiation of some purified polypeptide hormones and their biological and radioimmunological activity

International Nuclear Information System (INIS)

Hromadova, M.; Macho, L.; Strbak, V.; Vigas, M.; Mikulaj, L.

1979-01-01

Some polypeptide hormones (adrenocorticotropin - ACTH, human and bovine growth hormone - GH, human menopausal gonadotropin - HMG, human luteinizing hormone - LH, and bovine thyrotropin - TSH) were irradiated either with 2.5 or 12.5 Mrad (1.1 Mrad/h) or both and their biological activity or immunoreactivity was tested within few days or 3 to 5 months after irradiation. Biological activity of irradiated ACTH (estimation of corticosterone released into medium by incubated adrenals - Saffran and Schally 1955) was not decreased in both time intervals tested. Ten days after irradiation of bovine GH no changes in biological activity (tibia test - Wilhelmi 1973) were found. No decrease of biological activity of irradiated HMG (augmentation of ovarian and uterine weight - Butt 1973) was found 4 months after irradiation and, finaly, no decrease of bovine TSH activity (radioiodine release from prelabelled thyroid in mice - McKenzie 1958) was found 2 to 30 days after irradiation with 2.5 Mrad, while a decrease was observed after 12.5 Mrad. Three to five months after irradiation, however, there was a decrease of biological activity after both doses. The immunological reactivity of irradiated HMG and LH did not differ from that of nonirradiated samples. The same was found with human GH after 2.5 Mrad, while a decrease of reactivity after 12.5 Mrad was detected. It was concluded that, in most of cases, the sterilizing dose of gamma radiation (2.5 Mrad) did not affect the biological activity of polypeptide hormones and that their sensitivity to irradiation appears to differ. (author)

Bone health history in breast cancer patients on aromatase inhibitors.

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Marilyn L Kwan

Full Text Available A cross-sectional study was performed to assess bone health history among aromatase inhibitor (AI users before breast cancer (BC diagnosis, which may impact fracture risk after AI therapy and choice of initial hormonal therapy. A total of 2,157 invasive BC patients initially treated with an AI were identified from a prospective cohort study at Kaiser Permanente Northern California (KPNC. Data on demographic and lifestyle factors were obtained from in-person interviews, and bone health history and clinical data from KPNC clinical databases. The prevalence of osteoporosis and fractures in postmenopausal AI users was assessed, compared with 325 postmenopausal TAM users. The associations of bone health history with demographic and lifestyle factors in AI users were also examined. Among all initial AI users, 11.2% had a prior history of osteoporosis, 16.3% had a prior history of any fracture, and 4.6% had a prior history of major fracture. Postmenopausal women who were taking TAM as their initial hormonal therapy had significantly higher prevalence of prior osteoporosis than postmenopausal AI users (21.5% vs. 11.8%, p<0.0001. Among initial AI users, the associations of history of osteoporosis and fracture in BC patients with demographic and lifestyle factors were, in general, consistent with those known in healthy older women. This study is one of the first to characterize AI users and risk factors for bone morbidity before BC diagnosis. In the future, this study will examine lifestyle, molecular, and genetic risk factors for AI-induced fractures.

Advances in breast cancer treatment and prevention: preclinical studies on aromatase inhibitors and new selective estrogen receptor modulators (SERMs)

International Nuclear Information System (INIS)

Schiff, Rachel; Chamness, Gary C; Brown, Powel H

2003-01-01

Intensive basic and clinical research over the past 20 years has yielded crucial molecular understanding into how estrogen and the estrogen receptor act to regulate breast cancer and has led to the development of more effective, less toxic, and safer hormonal therapy agents for breast cancer management and prevention. Selective potent aromatase inhibitors are now challenging the hitherto gold standard of hormonal therapy, the selective estrogen-receptor modulator tamoxifen. Furthermore, new selective estrogen-receptor modulators such as arzoxifene, currently under clinical development, offer the possibility of selecting one with a more ideal pharmacological profile for treatment and prevention of breast cancer. Two recent studies in preclinical model systems that evaluate mechanisms of action of these new drugs and suggestions about their optimal clinical use are discussed

Review of the genus Ipomoea: traditional uses, chemistry and biological activities

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Marilena Meira

Full Text Available Approximately 600-700 species of Ipomoea, Convolvulaceae, are found throughout tropical and subtropical regions of the world. Several of those species have been used as ornamental plants, food, medicines or in religious ritual. The present work reviews the traditional uses, chemistry and biological activities of Ipomoea species and illustrates the potential of the genus as a source of therapeutic agents. These species are used in different parts of the world for the treatment of several diseases, such as, diabetes, hypertension, dysentery, constipation, fatigue, arthritis, rheumatism, hydrocephaly, meningitis, kidney ailments and inflammations. Some of these species showed antimicrobial, analgesic, spasmolitic, spasmogenic, hypoglycemic, hypotensive, anticoagulant, anti-inflammatory, psychotomimetic and anticancer activities. Alkaloids, phenolics compounds and glycolipids are the most common biologically active constituents from these plant extracts.

Synthesis, Physical Characterization and Biological Activity of Some Schiff Base Complexes

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R. Rajavel

2008-01-01

Full Text Available Structural modification of organic molecule has considerable biological relevance. Further, coordination of a biomolecules to the metal ions significantly alters the effectiveness of the biomolecules. In view of the antimicrobial activity ligand [bis-(2-aminobenzaldehyde] malonoyl dihydrazone], metal complexes with Cu(II, Ni(II, Zn(II and oxovanadium(IV have been synthesized and found to be potential antimicrobial agents. An attempt is also made to correlate the biological activities with geometry of the complexes. The complexes have been characterized by elemental analysis, molar conductance, spectra and cyclicvoltammetric measurements. The structural assessment of the complexes has been carried out based on electronic, infrared and molar conductivity values.

Isolation and characterization of biologically active venom protein from sea snake Enhydrina schistosa.

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Damotharan, Palani; Veeruraj, Anguchamy; Arumugam, Muthuvel; Balasubramanian, Thangavel

2015-03-01

The present study is designed to investigate the isolation and characterization of biological and biochemical active venom protein from sea snake, Enhydrina schistosa. The highest purification peaks in ion-exchange chromatography on DEAE-cellulose column were obtained for fraction numbers 39-49 when eluted with 0.35-0.45 M NaCl. Eighty per cent purity was obtained in the final stage of purification, and a single protein band of about 44 kDa was visualized in SDS-polyacrylamide gel under reducing condition. Purified venom protein expressed as haemolytic, cytotoxicity and proteolytic activities with lethal concentration (LC50 ) at 2.0 μg/mL. Venom protein exhibits enzymatic activity and hydrolyzed casein and gelatin. Gelatinolytic activity was optimal at pH 5-9. In conclusion, the present results suggested that the sea snake venom might be feasible sources for biologically active substances. Thus, this low molecular weight component of the venom protein could be used in potentially serve biological and pharmaceutical aspects. © 2014 Wiley Periodicals, Inc.

Yellow-Cedar, Callitropsis (Chamaecyparis) nootkatensis, Secondary Metabolites, Biological Activities, and Chemical Ecology.

Science.gov (United States)

Karchesy, Joseph J; Kelsey, Rick G; González-Hernández, M P

2018-05-01

Yellow-cedar, Callitropsis nootkatensis, is prevalent in coastal forests of southeast Alaska, western Canada, and inland forests along the Cascades to northern California, USA. These trees have few microbial or animal pests, attributable in part to the distinct groups of biologically active secondary metabolites their tissues store for chemical defense. Here we summarize the new yellow-cedar compounds identified and their biological activities, plus new or expanded activities for tissues, extracts, essential oils and previously known compounds since the last review more than 40 years ago. Monoterpene hydrocarbons are the most abundant compounds in foliage, while heartwood contains substantial quantities of oxygenated monoterpenes and oxygenated sesquiterpenes, with one or more tropolones. Diterpenes occur in foliage and bark, whereas condensed tannins have been isolated from inner bark. Biological activities expressed by one or more compounds in these groups include fungicide, bactericide, sporicide, acaricide, insecticide, general cytotoxicity, antioxidant and human anticancer. The diversity of organisms impacted by whole tissues, essential oils, extracts, or individual compounds now encompasses ticks, fleas, termites, ants, mosquitoes, bacteria, a water mold, fungi and browsing animals. Nootkatone, is a heartwood component with sufficient activity against arthropods to warrant research focused toward potential development as a commercial repellent and biopesticide for ticks, mosquitoes and possibly other arthropods that vector human and animal pathogens.

Fabrication, Characterization, and Biological Activity of Avermectin Nano-delivery Systems with Different Particle Sizes

Science.gov (United States)

Wang, Anqi; Wang, Yan; Sun, Changjiao; Wang, Chunxin; Cui, Bo; Zhao, Xiang; Zeng, Zhanghua; Yao, Junwei; Yang, Dongsheng; Liu, Guoqiang; Cui, Haixin

2018-01-01

Nano-delivery systems for the active ingredients of pesticides can improve the utilization rates of pesticides and prolong their control effects. This is due to the nanocarrier envelope and controlled release function. However, particles containing active ingredients in controlled release pesticide formulations are generally large and have wide size distributions. There have been limited studies about the effect of particle size on the controlled release properties and biological activities of pesticide delivery systems. In the current study, avermectin (Av) nano-delivery systems were constructed with different particle sizes and their performances were evaluated. The Av release rate in the nano-delivery system could be effectively controlled by changing the particle size. The biological activity increased with decreasing particle size. These results suggest that Av nano-delivery systems can significantly improve the controllable release, photostability, and biological activity, which will improve efficiency and reduce pesticide residues.

Screening of some marine plants from the Indian coast for biological activity

Digital Repository Service at National Institute of Oceanography (India)

Naqvi, S.W.A.; Solimabi; Kamat, S.Y.; DeSouza, L.; Reddy, C.V.G.; Bhakuni, D.S.; Dhawan, B.N.

Extracts of twenty five seaweeds from Indian coast have been put through a broad biological screen which includes tests for antiviral, antibacterial, antifungal, antiprotozoal, antifertility activities and a wide range of pharmacological activities...

Natural products as a resource for biologically active compounds

International Nuclear Information System (INIS)

Hanke, F.J.

1986-01-01

The goal of this study was to investigate various sources of biologically active natural products in an effort to identify the active pesticidal compounds involved. The study is divided into several parts. Chapter 1 contains a discussion of several new compounds from plant and animal sources. Chapter 2 introduces a new NMR technique. In section 2.1 a new technique for better utilizing the lanthanide relaxation agent Gd(fod) 3 is presented which allows the predictable removal of resonances without line broadening. Section 2.2 discusses a variation of this technique for use in an aqueous solvent by applying this technique towards identifying the binding sites of metals of biological interest. Section 2.3 presents an unambiguous 13 C NMR assignment of melibiose. Chapter 3 deals with work relating to the molting hormone of most arthropods, 20-hydroxyecdysone. Section 3.1 discusses the use of two-dimensional NMR (2D NMR) to assign the 1 H NMR spectrum of this biologically important compound. Section 3.2 presents a new application for Droplet countercurrent chromatography (DCCC). Chapter 4 presents a basic improvement to the commercial DCCC instrument that is currently being applied to future commercial instruments. Chapter 5 discusses a curious observation of the effects that two previously known compounds, nagilactone C and (-)-epicatechin, have on lettuce and rice and suggest a possible new role for the ubiquitous flavanol (-)-epicatechin in plants

Certification of biological reference materials by instrumental neutron activation analysis

International Nuclear Information System (INIS)

Lanjewar, Mamata R.; Lanjewar, R.B.

2014-01-01

A multielemental instrumental neutron activation analysis (INAA) method by short and long irradiation has been employed for the determination of 21 minor and trace elements in two standard Reference Materials P-RBF and P-WBF from Institute of Radioecology and Applied Nuclear Techniques ,Czechoslovakia. Also some biological standards such as Bowen's kale, cabbage leaves (Poland) including wheat and rice flour samples of local origin were analysed. It is suggested that INAA is an ideal method for the certification of Reference Materials of Biological Matrices. (author)

Biological activities of extracts from Chenopodium ambrosioides Lineu and Kielmeyera neglecta Saddi

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Sousa Zulane

2012-07-01

Full Text Available Abstract Background Chenopodium ambrosioides and Kielmeyera neglecta are plants traditionally used in Brazil to treat various infectious diseases. The study of the biological activities of these plants is of great importance for the detection of biologically active compounds. Methods Extracts from these plants were extracted with hexane (Hex, dichloromethane (DCM, ethyl acetate (EtOAc and ethanol (EtOH and assessed for their antimicrobial properties, bioactivity against Artemia salina Leach and antifungal action on the cell wall of Neurospora crassa. Results Extracts from C. ambrosioides (Hex, DCM and EtOH and K. neglecta (EtOAc and EtOH showed high bioactivity against A. salina (LD50 C. ambrosioides Hex and DCM showed specific activity against yeasts, highlighting the activity of hexanic extract against Candida krusei (MIC = 100 μg/mL. By comparing the inhibitory concentration of 50% growth (IC 50% with the growth control, extracts from K. neglecta EtOAc and EtOH have shown activities against multidrug-resistant bacteria (Enterococcus faecalis ATCC 51299 and Staphylococcus aureus ATCC 43300, with IC 50% of 12.5 μg/mL The assay carried out on N. crassa allowed defining that extracts with antifungal activity do not have action through inhibition of cell wall synthesis. Conclusions Generally speaking, extracts from C. ambrosioides and K. neglecta showed biological activities that have made the search for bioactive substances in these plants more attractive, illustrating the success of their use in the Brazilian folk medicine.

Neutron activation analysis of biological material

International Nuclear Information System (INIS)

Kucera, J.; Simkova, M.; Obrusnik, I.

1985-01-01

The possibilities are briefly summed up of usino. NAA (neutron activation analysis) for determining element traces in foodstuffs and their intake by organisms, for monitoring changes in the content of important trace elements in tissues and body fluids owing to environmental pollution, for verifying the results of other analytical techniques and for certifying the content of element traces in reference materials. Examples are given of the use of NAA, and the results are summed up of the determination of Cd, Mn and Zn in biological reference materials NBS SRM-1577, Bovine Liver, Bowen's Kale, IAEA Milk Powder A-11 and IAEA Animal Muscle H-4. (E.S.)

Generation of structurally novel short carotenoids and study of their biological activity

DEFF Research Database (Denmark)

Kim, Se Hyeuk; Kim, Moon S.; Lee, Bun Y.

2016-01-01

Recent research interest in phytochemicals has consistently driven the efforts in the metabolic engineering field toward microbial production of various carotenoids. In spite of systematic studies, the possibility of using C30 carotenoids as biologically functional compounds has not been explored...... thus far. Here, we generated 13 novel structures of C30 carotenoids and one C35 carotenoid, including acyclic, monocyclic, and bicyclic structures, through directed evolution and combinatorial biosynthesis, in Escherichia coli. Measurement of radical scavenging activity of various C30 carotenoid...... structures revealed that acyclic C30 carotenoids showed higher radical scavenging activity than did DL-atocopherol. We could assume high potential biological activity of the novel structures of C30 carotenoids as well, based on the neuronal differentiation activity observed for the monocyclic C30 carotenoid...

Preparation of Gc protein-derived macrophage activating factor (GcMAF) and its structural characterization and biological activities.

Science.gov (United States)

Mohamad, Saharuddin Bin; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

2002-01-01

Gc protein has been reported to be a precursor of Gc protein-derived macrophage activation factor (GcMAF) in the inflammation-primed macrophage activation cascade. An inducible beta-galactosidase of B cells and neuraminidase of T cells convert Gc protein to GcMAF. Gc protein from human serum was purified using 25(OH)D3 affinity column chromatography and modified to GcMAF using immobilized glycosidases (beta-galactosidase and neuraminidase) The sugar moiety structure of GcMAF was characterized by lectin blotting by Helix pomatia agglutinin. The biological activities of GcMAF were evaluated by a superoxide generation assay and a phagocytosis assay. We successfully purified Gc protein from human serum. GcMAF was detected by lectin blotting and showed a high biological activity. Our results support the importance of the terminal N-acetylgalactosamine moiety in the GcMAF-mediated macrophage activation cascade, and the existence of constitutive GcMAF in human serum. These preliminary data are important for designing small molecular GcMAF mimics.

Investigating Biological Activity Spectrum for Novel Styrylquinazoline Analogues

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Jaroslaw Polanski

2009-10-01

Full Text Available In this study, series of ring-substituted 2-styrylquinazolin-4(3H-one and 4-chloro-2-styrylquinazoline derivatives were prepared. The syntheses of the discussed compounds are presented. The compounds were analyzed by RP-HPLC to determine lipophilicity. They were tested for their inhibitory activity on photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial strains and against eight fungal strains. Several compounds showed biological activity comparable with or higher than that of the standard isoniazid. It was found that the electronic properties of the R substituent, and not the total lipophilicity of the compound, were decisive for the photosynthesis-inhibiting activity of tested compounds.

TOPICAL REVIEW: Protein stability and enzyme activity at extreme biological temperatures

Science.gov (United States)

Feller, Georges

2010-08-01

Psychrophilic microorganisms thrive in permanently cold environments, even at subzero temperatures. To maintain metabolic rates compatible with sustained life, they have improved the dynamics of their protein structures, thereby enabling appropriate molecular motions required for biological activity at low temperatures. As a consequence of this structural flexibility, psychrophilic proteins are unstable and heat-labile. In the upper range of biological temperatures, thermophiles and hyperthermophiles grow at temperatures > 100 °C and synthesize ultra-stable proteins. However, thermophilic enzymes are nearly inactive at room temperature as a result of their compactness and rigidity. At the molecular level, both types of extremophilic proteins have adapted the same structural factors, but in opposite directions, to address either activity at low temperatures or stability in hot environments. A model based on folding funnels is proposed accounting for the stability-activity relationships in extremophilic proteins.

Chemical Structure-Biological Activity Models for Pharmacophores’ 3D-Interactions

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Mihai V. Putz

2016-07-01

Full Text Available Within medicinal chemistry nowadays, the so-called pharmaco-dynamics seeks for qualitative (for understanding and quantitative (for predicting mechanisms/models by which given chemical structure or series of congeners actively act on biological sites either by focused interaction/therapy or by diffuse/hazardous influence. To this aim, the present review exposes three of the fertile directions in approaching the biological activity by chemical structural causes: the special computing trace of the algebraic structure-activity relationship (SPECTRAL-SAR offering the full analytical counterpart for multi-variate computational regression, the minimal topological difference (MTD as the revived precursor for comparative molecular field analyses (CoMFA and comparative molecular similarity indices analysis (CoMSIA; all of these methods and algorithms were presented, discussed and exemplified on relevant chemical medicinal systems as proton pump inhibitors belonging to the 4-indolyl,2-guanidinothiazole class of derivatives blocking the acid secretion from parietal cells in the stomach, the 1-[(2-hydroxyethoxy-methyl]-6-(phenylthiothymine congeners’ (HEPT ligands antiviral activity against Human Immunodeficiency Virus of first type (HIV-1 and new pharmacophores in treating severe genetic disorders (like depression and psychosis, respectively, all involving 3D pharmacophore interactions.

Biological regeneration of phenol-loaded activated carbon (up flow system)

International Nuclear Information System (INIS)

Durrani, M.A.Q.J.; Mirajuddin; Martin, R.J.

1995-01-01

This paper represents the report on the biological regeneration of totally activated carbon following the experimental studies carried out at the University of Birmingham, U.K. Biological regeneration is one of several methods that may be used to restore the adsorptive capacity of exhausted granular activated carbon. This study deals with in situ biological regeneration on a pilot scale. The principal objective of this research was to ascertain whether biological regeneration of GAC could occur under conditions typical of water treatment. The important parameters which may have the greatest impact on bio regeneration for a given adsorbate were studied. The research investigated the extent of bio regeneration for phenol of concentration 50 mg/l. Bio regeneration in the total exhaustion system was evaluated in terms of regeneration efficiency and the substrate removal. A three mode procedure was followed for each bio regeneration run. The prepared carbon was initialing exhausted with an adsorbate; it was then bio regenerated with a mixed culture of bacteria, and lastly the carbon was saturated. In the totally exhausted GAC system, the bio regeneration was enhanced by increasing the duration of regeneration for a fixed initial biomass content of the bioreactor. The regenerated phenol loaded GAC bed had nearly gained its original adsorption after the 5-day period of regeneration. Bacterial counts in the effluents of regenerated GAC columns were significantly more than those of fresh carbon effluents. (author)

Activation analysis of biological materials at the Activation Analysis Centre

International Nuclear Information System (INIS)

Kukula, F.; Obrusnik, I.; Simkova, M.; Kucera, J.; Krivanek, M.

1976-01-01

A review is presented of the work of the Activation Analysis Centre of the Nuclear Research Institute for different fields of the Czechoslovak economy, aimed primarily at analyzing biological materials with the purpose of determining the contents of the so-called vital trace elements and of elements which already have a toxic effect on the organism in trace concentrations. Another important field of research is the path of trace elements from the environment to the human organism. A destructive method for the simultaneous determination of 12 trace elements in 11 kinds of human tissue has been studied. (Z.M.)

Determination of chromium in biological matrices by neutron activation

International Nuclear Information System (INIS)

McClendon, L.T.

1978-01-01

Chromium is recognized to be an essential trace element in several biological systems. It exists in many biological materials in a variety of chemical forms and very low concentration levels which cause problems for many analytical techniques. Both instrumental and destructive neutron activation analysis were used to determine the chromium concentration in Orchard Leaves, SRM 1571, Brewers Yeast, SRM 1569, and Bovine Liver, SRM 1577. Some of the problems inherent with determining chromium in certain biological matrices and the data obtained here at the National Bureau of Standards using this technique are discussed. The results obtained from dissolution of brewers yeast in a closed system as described in the DNAA procedure are in good agreement with the INAA results. The same phenomenon existed in the determination of chromium in bovine liver. The radiochemical procedure described for chromium (DNAA) provides the analyst with a simple, rapid and selective technique for chromium determination in a variety of matrices. (T.G.)

Expression of biologically active murine interleukin-18 in Lactococcus lactis.

Science.gov (United States)

Feizollahzadeh, Sadegh; Khanahmad, Hossein; Rahimmanesh, Ilnaz; Ganjalikhani-Hakemi, Mazdak; Andalib, Alireza; Sanei, Mohammad Hossein; Rezaei, Abbas

2016-11-01

The food-grade bacterium Lactococcus lactis is increasingly used for heterologous protein expression in therapeutic and industrial applications. The ability of L. lactis to secrete biologically active cytokines may be used for the generation of therapeutic cytokines. Interleukin (IL)-18 enhances the immune response, especially on mucosal surfaces, emphasizing its therapeutic potential. However, it is produced as an inactive precursor and has to be enzymatically cleaved for maturation. We genetically manipulated L. lactis to secrete murine IL-18. The mature murine IL-18 gene was inserted downstream of a nisin promoter in pNZ8149 plasmid and the construct was used to transform L. lactis NZ3900. The transformants were selected on Elliker agar and confirmed by restriction enzyme digestion and sequencing. The expression and secretion of IL-18 protein was verified by SDS-PAGE, western blotting and ELISA. The biological activity of recombinant IL-18 was determined by its ability to induce interferon (IFN)-γ production in L. lactis co-cultured with murine splenic T cells. The amounts of IL-18 in bacterial lysates and supernatants were 3-4 μg mL -1 and 0.6-0.7 ng mL -1 , respectively. The successfully generated L. lactis strain that expressed biologically active murine IL-18 can be used to evaluate the possible therapeutic effects of IL-18 on mucosal surfaces. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Myricetin: A Dietary Molecule with Diverse Biological Activities

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Deepak Kumar Semwal

2016-02-01

Full Text Available Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson’s and Alzheimer’s. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound’s ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities.

The genus Scrophularia: a source of iridoids and terpenoids with a diverse biological activity.

Science.gov (United States)

Pasdaran, Ardalan; Hamedi, Azadeh

2017-12-01

Scrophularia genus (Scrophulariaceae) includes about 350 species commonly known as figwort. Many species of this genus grow wild in nature and have not been cultivated yet. However, some species are in danger of extinction. This paper reviews the chemical compounds, biological activities and the ethnopharmacology of some Scrophularia species. All information was obtained through reported data on bibliographic database such as Scopus, United States National Agricultural Library, Biological Abstracts, EMBASE, PubMed, MedlinePlus, PubChem and Springer Link (1934-2017). The information in different Pharmacopoeias on this genus was also gathered from 1957 to 2007. The structures of 204 compounds and their biological activity were presented in the manuscript: glycoside esters, iridoid glycosides and triterpenoids are the most common compounds in this genus. Among them, scropolioside like iridoids have shown potential for anti-inflammatory, hepatoprotective and wound healing activity. Among the less frequently isolated compounds, resin glycosides such as crypthophilic acids have shown potent antiprotozoal and antimicrobial activities. The Scrophularia genus seems to be a rich source of iridoids and terpenoids, but isolation and identification of its alkaloids have been a neglected area of scientific study. The diverse chemical compounds and biological activities of this genus will motivate further investigation on Scrophularia genus as a source of new therapeutic medications.

A systematic review and methodological evaluation of published cost-effectiveness analyses of aromatase inhibitors versus tamoxifen in early stage breast cancer.

Directory of Open Access Journals (Sweden)

Ava A John-Baptiste

Full Text Available BACKGROUND: A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs. For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs of five years of aromatase inhibitors (AI versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS but not overall survival (OS and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. METHODS: We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY. We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. RESULTS: We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. CONCLUSION: Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs

Milk kefir: composition, microbial cultures, biological activities, and related products.

Science.gov (United States)

Prado, Maria R; Blandón, Lina Marcela; Vandenberghe, Luciana P S; Rodrigues, Cristine; Castro, Guillermo R; Thomaz-Soccol, Vanete; Soccol, Carlos R

2015-01-01

In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir's exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir's microflora and the importance of kefiran as a beneficial health substance.

Biological activities and biomedical potential of sea cucumber (Stichopus japonicus: a review

Directory of Open Access Journals (Sweden)

Gun-Woo Oh

2017-11-01

Full Text Available Abstract Members of the phylum Echinodermata, commonly known as echinoderms, are exclusively marine invertebrates. Among the Echinodermata, sea cucumber belongs to the family Holothuroidea. The sea cucumber Stichopus (Apostichous japonicus (Selenka is an invertebrate animal inhabiting the coastal sea around Korean, Japan, China, and Russia. Sea cucumber has a significant commercial value, because it contains valuable nutrients such as vitamins and minerals. They possess a number of distinctive biologically and pharmacologically important compounds. In particular, the body wall of sea cucumber is a major edible part. It consists of peptide, collagen, gelatin, polysaccharide, and saponin, which possess several biological activities such as anti-cancer, anti-coagulation, anti-oxidation, and anti-osteoclastogenesis. Furthermore, the regenerative capacity of sea cucumber makes it a medically important organism. This review presents the various biological activities and biomedical potential of sea cucumber S. japonicus.

Biological conversion system

Science.gov (United States)

Scott, C.D.

A system for bioconversion of organic material comprises a primary bioreactor column wherein a biological active agent (zymomonas mobilis) converts the organic material (sugar) to a product (alcohol), a rejuvenator column wherein the biological activity of said biological active agent is enhanced, and means for circulating said biological active agent between said primary bioreactor column and said rejuvenator column.

Polysaccharies of higher fungi: Biological role, structure and antioxidative activity

NARCIS (Netherlands)

Kozarski, M.S.; Klaus, A.; Niksic, M.; Griensven, van L.J.L.D.; Vrvic, M.M.; Jakovljevic, D.M.

2014-01-01

The fungal polysaccharides attract a lot of attention due to their multiple challenging bio-logical properties, such as: anti-tumor, anti-viral, anticomplementary, anticoagulant, hypo-lipidemic, immunomodulatory and immune-stimulatory activities, which all together make them suitable for application

Preparation and characterization of new biologically active polyurethane foams.

Science.gov (United States)

Savelyev, Yuri; Veselov, Vitali; Markovskaya, Ludmila; Savelyeva, Olga; Akhranovich, Elena; Galatenko, Natalya; Robota, Ludmila; Travinskaya, Tamara

2014-12-01

Biologically active polyurethane foams are the fast-developed alternative to many applications of biomedical materials. Due to the polyurethane structure features and foam technology it is possible to incorporate into their structure the biologically active compounds of target purpose via structural-chemical modification of macromolecule. A series of new biologically active polyurethane foams (PUFs) was synthesized with polyethers (MM 2500-5000), polyesters MM (500-2200), 2,4(2,6) toluene diisocyanate, water as a foaming agent, catalysts, foam stabilizers and functional compounds. Different functional compounds: 1,4-di-N-oxy-2,3-bis-(oxymethyl)-quinoxaline (DOMQ), partial sodium salt of poly(acrylic acid) and 2,6-dimethyl-N,N-diethyl aminoacetatanilide hydrochloride were incorporated into the polymer structure/composition due to the chemical and/or physical bonding. Structural peculiarities of PUFs were studied by FTIR spectroscopy and X-ray scattering. Self-adhesion properties of PUFs were estimated by measuring of tensile strength at break of adhesive junction. The optical microscopy method was performed for the PUF morphology studies. Toxicological estimation of the PUFs was carried out in vitro and in vivo. The antibacterial action towards the Gram-positive and Gram-negative bacteria (Escherichia coli ATC 25922, E. coli ATC 2150, Klebsiella pneumoniae 6447, Staphylococcus aureus 180, Pseudomonas aeruginosa 8180, Proteus mirabilis F 403, P. mirabilis 6054, and Proteus vulgaris 8718) was studied by the disc method on the solid nutrient. Physic-chemical properties of the PUFs (density, tensile strength and elongation at break, water absorption and vapor permeability) showed that all studied PUFs are within the operational requirements for such materials and represent fine-cellular foams. Spectral studies confirmed the incorporation of DOMQ into the PUF's macrochain. PUFs are characterized by microheterogeneous structure. They are antibacterially active, non

A study on biological activity of marine fungi from different habitats in coastal regions.

Science.gov (United States)

Zhou, Songlin; Wang, Min; Feng, Qi; Lin, Yingying; Zhao, Huange

2016-01-01

In recent years, marine fungi have become an important source of active marine natural products. Former researches are limited in habitats selection of fungi with bioactive compounds. In this paper were to measure antibacterial and antitumor cell activity for secondary metabolites of marine fungi, which were isolated from different habitats in coastal regions. 195 strains of marine fungi were isolated and purified from three different habitats. They biologically active experiment results showed that fungi isolation from the mangrove habitats had stronger antibacterial activity than others, and the stains isolated from the estuarial habitats had the least antibacterial activity. However, the strains separated from beach habitats strongly inhibited tumor cell proliferation in vitro, and fungi of mangrove forest habitats had the weakest activity of inhibiting tumor. Meanwhile, 195 fungal strains belonged to 46 families, 84 genera, 142 species and also showed 137 different types of activity combinations by analyzing the inhibitory activity of the metabolites fungi for 4 strains of pathogenic bacteria and B-16 cells. The study investigated the biological activity of marine fungi isolated from different habitats in Haikou coastal regions. The results help us to understand bioactive metabolites of marine fungi from different habitats, and how to selected biological activity fungi from various marine habitats effectively.

Comparative study on individual aromatase inhibitors on cardiovascular safety profile: a network meta-analysis

Science.gov (United States)

Zhao, Xihe; Liu, Lei; Li, Kai; Li, Wusheng; Zhao, Li; Zou, Huawei

2015-01-01

The third-generation aromatase inhibitors (AIs: anastrozole, letrozole, and exemestane) have now become standard adjuvant endocrine treatment for postmenopausal estrogen receptor-positive breast cancer complementing chemotherapy and surgery. Because of the absence of direct head-to-head comparisons of these AIs, an indirect comparison is needed for individual treatment choice. In this network systemic assessment, the cardiovascular (CV) side effects in using anastrozole, letrozole, and exemestane based on original studies on AIs vs placebo or tamoxifen were compared. We integrated all available direct and indirect evidences. The odds ratio (OR) of severe CV events for indirect comparisons between exemestane and anastrozole was 1.41 (95% confidence interval [CI] =0.49–2.78), letrozole and anastrozole was 1.80 (95% CI =0.40–3.92), and letrozole and exemestane was 1.46 (95% CI =0.34–3.4). OR of subgroup risk for AIs and tamoxifen were all >1 except for thrombolism risk subgroup. The results showed that the total and severe CV risk ranking is letrozole, exemestane, and anastrozole in descending order. None of the AIs showed advantages in CV events than tamoxifen except for thromboembolism event incidence. PMID:26491345

Are previous episodes of bacterial vaginosis a predictor for vaginal symptoms in breast cancer patients treated with aromatase inhibitors?

DEFF Research Database (Denmark)

Gade, Malene R; Goukasian, Irina; Panduro, Nathalie

2018-01-01

Objective To estimate the prevalence of vaginal symptoms in postmenopausal women with breast cancer exposed to aromatase inhibitors, and to investigate if the risk of vaginal symptoms is associated with previous episodes of bacterial vaginosis. Methods Patients from Rigshospitalet and Herlev...... University Hospital, Denmark, were identified through the register of Danish Breast Cancer Cooperation Group and 78 patients participated in the study. Semiquantitave questionnaires and telephone interview were used to assess the prevalence of vaginal symptoms and previous episode(s) of bacterial vaginosis....... Multivariable logistic regression models were used to assess the association between vaginal symptoms and previous episodes of bacterial vaginosis. Results Moderate to severe symptoms due to vaginal itching/irritation were experienced by 6.4% (95% CI: 2.8-14.1%), vaginal dryness by 28.4% (95% CI: 19...

Urine: Waste product or biologically active tissue?

Science.gov (United States)

2018-03-01

Historically, urine has been viewed primarily as a waste product with little biological role in the overall health of an individual. Increasingly, data suggest that urine plays a role in human health beyond waste excretion. For example, urine might act as an irritant and contribute to symptoms through interaction with-and potential compromise of-the urothelium. To explore the concept that urine may be a vehicle for agents with potential or occult bioactivity and to discuss existing evidence and novel research questions that may yield insight into such a role, the National Institute of Diabetes and Digestive and Kidney Disease invited experts in the fields of comparative evolutionary physiology, basic science, nephrology, urology, pediatrics, metabolomics, and proteomics (among others) to a Urinology Think Tank meeting on February 9, 2015. This report reflects ideas that evolved from this meeting and current literature, including the concept of urine quality, the biological, chemical, and physical characteristics of urine, including the microbiota, cells, exosomes, pH, metabolites, proteins, and specific gravity (among others). Additionally, the manuscript presents speculative, and hopefully testable, ideas about the functional roles of urine constituents in health and disease. Moving forward, there are several questions that need further understanding and pursuit. There were suggestions to consider actively using various animal models and their biological specimens to elaborate on basic mechanistic information regarding human bladder dysfunction. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells

International Nuclear Information System (INIS)

Lui, Asona; New, Jacob; Ogony, Joshua; Thomas, Sufi; Lewis-Wambi, Joan

2016-01-01

mTOR inhibition of aromatase inhibitor (AI)-resistant breast cancer is currently under evaluation in the clinic. Everolimus/RAD001 (Afinitor®) has had limited efficacy as a solo agent but is projected to become part of combination therapy for AI-resistant breast cancer. This study was conducted to investigate the anti-proliferative and resistance mechanisms of everolimus in AI-resistant breast cancer cells. In this study we utilized two AI-resistant breast cancer cell lines, MCF-7:5C and MCF-7:2A, which were clonally derived from estrogen receptor positive (ER+) MCF-7 breast cancer cells following long-term estrogen deprivation. Cell viability assay, colony formation assay, cell cycle analysis and soft agar anchorage-independent growth assay were used to determine the efficacy of everolimus in inhibiting the proliferation and tumor forming potential of MCF-7, MCF-7:5C, MCF-7:2A and MCF10A cells. Confocal microscopy and transmission electron microscopy were used to evaluate LC3-II production and autophagosome formation, while ERE-luciferase reporter, Western blot, and RT-PCR analyses were used to assess ER expression and transcriptional activity. Everolimus inhibited the proliferation of MCF-7:5C and MCF-7:2A cells with relatively equal efficiency to parental MCF-7 breast cancer cells. The inhibitory effect of everolimus was due to G1 arrest as a result of downregulation of cyclin D1 and p21. Everolimus also dramatically reduced estrogen receptor (ER) expression (mRNA and protein) and transcriptional activity in addition to the ER chaperone, heat shock protein 90 protein (HSP90). Everolimus restored 4-hydroxy-tamoxifen (4OHT) sensitivity in MCF-7:5C cells and enhanced 4OHT sensitivity in MCF-7 and MCF-7:2A cells. Notably, we found that autophagy is one method of everolimus insensitivity in MCF-7 breast cancer cell lines. This study provides additional insight into the mechanism(s) of action of everolimus that can be used to enhance the utility of mTOR inhibitors as

The chemical structures, plant origins, ethnobotany and biological activities of homoisoflavanones.

Science.gov (United States)

du Toit, Karen; Drewes, Siegfried E; Bodenstein, Johannes

2010-03-01

This work reviews the four basic structural types of homoisoflavanones. The relationships between the various structures of homoisoflavanones and their plant origins, ethnobotany and biological activities are put into perspective.

Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity

Czech Academy of Sciences Publication Activity Database

Novotná, E.; Waisser, K.; Kuneš, J.; Palát, K.; Skálová, L.; Szotáková, B.; Buchta, V.; Stolaříková, J.; Ulmann, V.; Pávová, Marcela; Weber, Jan; Komrsková, J.; Hašková, P.; Vokřál, I.; Wsól, V.

2017-01-01

Roč. 350, č. 8 (2017), č. článku e1700020. ISSN 0365-6233 Institutional support: RVO:61388963 Keywords : biological activity * cytotoxicity * isocitrate lyase * isothiosemicarbazone * tuberculosis Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 1.994, year: 2016

Comparison of growth methods and biological activities of brazilian marine Streptomyces

Directory of Open Access Journals (Sweden)

A. C. Granato

2013-03-01

Full Text Available The present work describes the study of the growth and the cytotoxic and antitumor activities of the extracts of the marine microorganisms Streptomyces acrymicini and Streptomyces cebimarensis, the latter a new strain. Both microorganisms were collected from coastal marine sediments of the north coast of São Paulo state. Growth was performed in a shaker and in a bioreactor using Gym medium and the broths of both microorganisms were extracted with ethyl acetate and n-butanol. Three extracts, two organic and one aqueous, from each microorganism were obtained and tested for cytotoxic and antitumor activity using the SF-295 (Central Nervous System, HCT-8 (Colon cell lines, and the MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide method. The growth methods were compared and show that, although the shaker presented reasonable results, the bioreactor represents the best choice for growth of these microorganisms. The biological activity of the different extracts was evaluated and it was demonstrated that the growth methodology may influence the secondary metabolite production and the biological activity.

Targeted Metabolomics Approach To Detect the Misuse of Steroidal Aromatase Inhibitors in Equine Sports by Biomarker Profiling.

Science.gov (United States)

Chan, George Ho Man; Ho, Emmie Ngai Man; Leung, David Kwan Kon; Wong, Kin Sing; Wan, Terence See Ming

2016-01-05

The use of anabolic androgenic steroids (AAS) is prohibited in both human and equine sports. The conventional approach in doping control testing for AAS (as well as other prohibited substances) is accomplished by the direct detection of target AAS or their characteristic metabolites in biological samples using hyphenated techniques such as gas chromatography or liquid chromatography coupled with mass spectrometry. Such an approach, however, falls short when dealing with unknown designer steroids where reference materials and their pharmacokinetics are not available. In addition, AASs with fast elimination times render the direct detection approach ineffective as the detection window is short. A targeted metabolomics approach is a plausible alternative to the conventional direct detection approach for controlling the misuse of AAS in sports. Because the administration of AAS of the same class may trigger similar physiological responses or effects in the body, it may be possible to detect such administrations by monitoring changes in the endogenous steroidal expression profile. This study attempts to evaluate the viability of using the targeted metabolomics approach to detect the administration of steroidal aromatase inhibitors, namely androst-4-ene-3,6,17-trione (6-OXO) and androsta-1,4,6-triene-3,17-dione (ATD), in horses. Total (free and conjugated) urinary concentrations of 31 endogenous steroids were determined by gas chromatography-tandem mass spectrometry for a group of 2 resting and 2 in-training thoroughbred geldings treated with either 6-OXO or ATD. Similar data were also obtained from a control (untreated) group of in-training thoroughbred geldings (n = 28). Statistical processing and chemometric procedures using principle component analysis and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) have highlighted 7 potential biomarkers that could be used to differentiate urine samples obtained from the control and the treated groups

Biological Activities of Phenolic Compounds of Extra Virgin Olive Oil

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Maurizio Servili

2013-12-01

Full Text Available Over the last few decades, multiple biological properties, providing antioxidant, anti-inflammatory, chemopreventive and anti-cancer benefits, as well as the characteristic pungent and bitter taste, have been attributed to Extra Virgin Olive Oil (EVOO phenols. In particular, growing efforts have been devoted to the study of the antioxidants of EVOO, due to their importance from health, biological and sensory points of view. Hydrophilic and lipophilic phenols represent the main antioxidants of EVOO, and they include a large variety of compounds. Among them, the most concentrated phenols are lignans and secoiridoids, with the latter found exclusively in the Oleaceae family, of which the drupe is the only edible fruit. In recent years, therefore, we have tackled the study of the main properties of phenols, including the relationships between their biological activity and the related chemical structure. This review, in fact, focuses on the phenolic compounds of EVOO, and, in particular, on their biological properties, sensory aspects and antioxidant capacity, with a particular emphasis on the extension of the product shelf-life.

MILK KEFIR: COMPOSITION, MICROBIAL CULTURES, BIOLOGICAL ACTIVITIES AND RELATED PRODUCTS

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Maria Rosa Prado

2015-10-01

Full Text Available In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir’s exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir’s microflora and the importance of kefiran as a beneficial health substance.

Comparative toxicity and endocrine disruption potential of urban and rural atmospheric organic PM1 in JEG-3 human placental cells

International Nuclear Information System (INIS)

Drooge, Barend L. van; Marqueño, Anna; Grimalt, Joan O.; Fernández, Pilar; Porte, Cinta

2017-01-01

Outdoor ambient air particulate matter and air pollution are related to adverse effects on human health. The present study assesses the cytotoxicity and ability to disrupt aromatase activity of organic PM 1 extracts from rural and urban areas at equivalent air volumes from 2 to 30 m 3 , in human placental JEG-3 cells. Samples were chemically analyzed for particle bounded organic compounds with endocrine disrupting potential, i.e. PAH, O-PAH, phthalate esters, but also for organic molecular tracer compounds for the emission source identification. Rural samples collected in winter were cytotoxic at the highest concentration tested and strongly inhibited aromatase activity in JEG-3 cells. No cytotoxicity was detected in summer samples from the rural site and the urban samples, while aromatase activity was moderately inhibited in these samples. In the urban area, the street site samples, collected close to intensive traffic, showed stronger inhibition of aromatase activity than the samples simultaneously collected at a roof site, 50 m above ground level. The cytotoxicity and endocrine disruption potential of the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning in the rural site in winter. - Highlights: • Organic extracts of outdoor ambient air PM1 showed aromatase activity inhibition in exposed human placental JEG-3 cells. • Cytotoxicity and strongest endocrine disruption was observed in rural winter samples, while lowest inhibition was observed in urban background site 50 m above a busy street. • Cytotoxicity and aromatase activity inhibition in the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning. - Organic extracts from ambient air PM 1 related to biomass burning are more cytotoxic and have stronger endocrine disruption potential than urban PM 1 .

Radiometric microbiologic assay for the biologically active forms of niacin

International Nuclear Information System (INIS)

Kertcher, J.A.; Guilarte, T.R.; Chen, M.F.; Rider, A.A.; McIntyre, P.A.

1979-01-01

A radiometric microbiologic assay has been developed for the determination of niacin in biologic fluids. Lactobacillus plantarum produced 14 CO 2 from L-[U- 14 C] malic acid in quantities proportional to the amount of niacin present. The assay is specific for the biologically active forms of niacin in humans. Thirty normal hemolysates were analyzed and the values ranged from 13.0 to 17.8 μg niacin/ml RBC (mean = 15.27 +- 1.33 s.d.). Good recovery and reproducibility studies were obtained with this assay. On thirty blood samples, correlation was excellent between the radiometric and the conventional turbidimetric assays

Binding of ferric ions is essential for the biological activity of glycine-extended gastrin

International Nuclear Information System (INIS)

Baldwin, G.S.; Pannequin, J.; Hollande, F.; Shulkes, A.

2002-01-01

Full text: Non-amidated gastrins, such as glycine-extended gastrin17 (Ggly), are now known to be biologically active. Ggly stimulates cell proliferation and migration, and was recently shown to bind two ferric ions with high affinity. The objective of the present work was to define the structure of Ggly for the first time, and to investigate the role of ferric ions in biological activity. Methods: The structure of Ggly, and the identity of the ammo acids that act as ferric ion ligands, were determined by NMR and fluorescence spectroscopy. The effect on the gastric epithelial cell line IMGE-5 of Ggly fragments, and of Ggy mutants with some or all of the five consecutive glutamate residues replaced by alanine, was measured in terms of cell proliferation, cell migration and phosphorylation of focal adhesion kinase. Results: Ggly adopts a well-defined loop stabilised by hydrophobic interactions between Leu5, Tyrl2, Trp 14 and Phe17. Studies with Ggly fragments indicated that ferric ions bind via the pentaglutamate sequence, which is necessary but not sufficient for full activity Selective replacement of some or all of the glutamates results in a reduction in ferric ion binding, and complete loss of biological activity. Conclusion: Our results are consistent with the hypothesis that ferric ion binding is necessary for biological activity

A Review on Chemical Constituents and Biological Activities of the ...

African Journals Online (AJOL)

The current review is aimed to deliver some updates on the ethnobotany, phytochemistry and biological activities of Beilschmiedia species in order to throw more light on their therapeutic potentials and future research priorities. Phytochemical studies on Beilschmiedia genus yielded essential oils, endiandric acid ...

Secondary Metabolites from Inula britannica L. and Their Biological Activities

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Yoon-Ha Kim

2010-03-01

Full Text Available Inula britannica L., family Asteraceae, is used in traditional Chinese and Kampo Medicines for various diseases. Flowers or the aerial parts are a rich source of secondary metabolites. These consist mainly of terpenoids (sesquiterpene lactones and dimmers, diterpenes and triterpenoids and flavonoids. The isolated compounds have shown diverse biological activities: anticancer, antioxidant, anti-inflammatory, neuroprotective and hepatoprotective activities. This review provides information on isolated bioactive phytochemicals and pharmacological potentials of I. britannica.

Gifted and Talented Students' Views about Biology Activities in a Science and Art Center

Science.gov (United States)

Özarslan, Murat; Çetin, Gülcan

2018-01-01

The aim of the study was to determine gifted and talented students' views about biology activities in a science and art center. The study was conducted with 26 gifted and talented students who studied at a science and art center in southwestern Turkey. Students studied animal and plant genus and species in biology activities. Data were collected…

Active Learning Not Associated with Student Learning in a Random Sample of College Biology Courses

Science.gov (United States)

Andrews, T. M.; Leonard, M. J.; Colgrove, C. A.; Kalinowski, S. T.

2011-01-01

Previous research has suggested that adding active learning to traditional college science lectures substantially improves student learning. However, this research predominantly studied courses taught by science education researchers, who are likely to have exceptional teaching expertise. The present study investigated introductory biology courses randomly selected from a list of prominent colleges and universities to include instructors representing a broader population. We examined the relationship between active learning and student learning in the subject area of natural selection. We found no association between student learning gains and the use of active-learning instruction. Although active learning has the potential to substantially improve student learning, this research suggests that active learning, as used by typical college biology instructors, is not associated with greater learning gains. We contend that most instructors lack the rich and nuanced understanding of teaching and learning that science education researchers have developed. Therefore, active learning as designed and implemented by typical college biology instructors may superficially resemble active learning used by education researchers, but lacks the constructivist elements necessary for improving learning. PMID:22135373

Complementary or alternative medicine as possible determinant of decreased persistence to aromatase inhibitor therapy among older women with non-metastatic breast cancer.

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Laetitia Huiart

Full Text Available PURPOSE: Aromatase inhibitor therapy (AI significantly improves survival in breast cancer patients. Little is known about adherence and persistence to aromatase inhibitors and about the causes of treatment discontinuation among older women. METHODS: We constituted a cohort of women over 65 receiving a first AI therapy for breast cancer between 2006 and 2008, and followed them until June 2011. Women were selected in the population-based French National Health Insurance databases, and data was collected on the basis of pharmacy refills, medical records and face-to-face interviews. Non-persistence to treatment was defined as the first treatment discontinuation lasting more than 3 consecutive months. Time to treatment discontinuation was studied using survival analysis techniques. RESULTS: Overall among the 382 selected women, non-persistence to treatment went from 8.7% (95%CI: 6.2-12.1 at 1 year, to 15.6% (95%CI: 12.2-19.8 at 2 years, 20.8% (95%CI: 16.7-25.6 at 3 years, and 24.7% (95%CI: 19.5-31.0 at 4 years. In the multivariate analysis on a sub-sample of 233 women with available data, women using complementary or alternative medicine (CAM (HR = 3.2; 95%CI: 1.5-6.9 or suffering from comorbidities (HR = 2.2; 95%CI: 1.0-4.8 were more likely to discontinue their treatment, whereas women with polypharmacy (HR = 0.4; 95%CI: 0.2-0.91 were less likely to discontinue. In addition, 13% of the women with positive hormonal receptor status did not fill any prescription for anti-hormonal therapy. CONCLUSION: AI therapy is discontinued prematurely in a substantial portion of older patients. Some patients may use CAM not as a complementary treatment, but as an alternative to conventional medicine. Improving patient-physician communication on the use of CAM may improve hormonal therapy adherence.

Complementary or alternative medicine as possible determinant of decreased persistence to aromatase inhibitor therapy among older women with non-metastatic breast cancer.

Science.gov (United States)

Huiart, Laetitia; Bouhnik, Anne-Deborah; Rey, Dominique; Rousseau, Frédérique; Retornaz, Frédérique; Meresse, Mégane; Bendiane, Marc Karim; Viens, Patrice; Giorgi, Roch

2013-01-01

Aromatase inhibitor therapy (AI) significantly improves survival in breast cancer patients. Little is known about adherence and persistence to aromatase inhibitors and about the causes of treatment discontinuation among older women. We constituted a cohort of women over 65 receiving a first AI therapy for breast cancer between 2006 and 2008, and followed them until June 2011. Women were selected in the population-based French National Health Insurance databases, and data was collected on the basis of pharmacy refills, medical records and face-to-face interviews. Non-persistence to treatment was defined as the first treatment discontinuation lasting more than 3 consecutive months. Time to treatment discontinuation was studied using survival analysis techniques. Overall among the 382 selected women, non-persistence to treatment went from 8.7% (95%CI: 6.2-12.1) at 1 year, to 15.6% (95%CI: 12.2-19.8) at 2 years, 20.8% (95%CI: 16.7-25.6) at 3 years, and 24.7% (95%CI: 19.5-31.0) at 4 years. In the multivariate analysis on a sub-sample of 233 women with available data, women using complementary or alternative medicine (CAM) (HR = 3.2; 95%CI: 1.5-6.9) or suffering from comorbidities (HR = 2.2; 95%CI: 1.0-4.8) were more likely to discontinue their treatment, whereas women with polypharmacy (HR = 0.4; 95%CI: 0.2-0.91) were less likely to discontinue. In addition, 13% of the women with positive hormonal receptor status did not fill any prescription for anti-hormonal therapy. AI therapy is discontinued prematurely in a substantial portion of older patients. Some patients may use CAM not as a complementary treatment, but as an alternative to conventional medicine. Improving patient-physician communication on the use of CAM may improve hormonal therapy adherence.

Allobetulin and Its Derivatives: Synthesis and Biological Activity

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Talgat S. Seitembetov

2011-03-01

Full Text Available This review covers the chemistry of allobetulin analogs, including their formation by rearrangement from betulin derivatives, their further derivatisation, their fusion with heterocyclic rings, and any further rearrangements of allobetulin compounds including ring opening, ring contraction and ring expansion reactions. In the last part, the most important biological activities of allobetulin derivatives are listed. One hundred and fifteen references are cited and the relevant literature is covered, starting in 1922 up to the end of 2010.

The cell biology of T-dependent B cell activation

DEFF Research Database (Denmark)

Owens, T; Zeine, R

1989-01-01

The requirement that CD4+ helper T cells recognize antigen in association with class II Major Histocompatibility Complex (MHC) encoded molecules constrains T cells to activation through intercellular interaction. The cell biology of the interactions between CD4+ T cells and antigen-presenting cells...... includes multipoint intermolecular interactions that probably involve aggregation of both polymorphic and monomorphic T cell surface molecules. Such aggregations have been shown in vitro to markedly enhance and, in some cases, induce T cell activation. The production of T-derived lymphokines that have been...... implicated in B cell activation is dependent on the T cell receptor for antigen and its associated CD3 signalling complex. T-dependent help for B cell activation is therefore similarly MHC-restricted and involves T-B intercellular interaction. Recent reports that describe antigen-independent B cell...

Effect of gamma irradiation on phenol content, antioxidant activity and biological activity of black maca and red maca extracts (Lepidium meyenii walp).

Science.gov (United States)

Zevallos-Concha, A; Nuñez, D; Gasco, M; Vasquez, C; Quispe, M; Gonzales, G F

2016-01-01

This study was performed to determine the effects of gamma irradiation on UV spectrum on maca, total content of polyphenols, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities and in vivo biological activities of red and black maca extracts (Lepidium meyenii). Adult mice of the strain Swiss aged 3 months and weighing 30-35 g in average were used to determine biological activities. Daily sperm production, effect on testosterone-induced prostate hyperplasia and forced swimming test were used to determine the effect of irradiation on biological activities of maca extracts. Irradiation did not show differences in UV spectrum but improves the amount of total polyphenols in red maca as well as in black maca extracts. In both cases, black maca extract has more content of polyphenols than red maca extract (p maca extract were administered to mice (p > 0.05). Black maca extract but not red maca extract has more swimming endurance capacity in the forced swimming test. Irradiation of black maca extract increased the swimming time to exhaustion (p maca extract (p > 0.05). Testosterone enanthate (TE) increased significantly the ventral prostate weight. Administration of red maca extract in animals treated with TE prevented the increase in prostate weight. Irradiation did not modify effect of red maca extract on prostate weight (p > 0.05). In conclusion, irradiation does not alter the biological activities of both black maca and red maca extracts. It prevents the presence of microorganisms in the extracts of black or red maca, but the biological activities were maintained.

Evaluating the biological activity of oil-polluted soils using a complex index

Science.gov (United States)

Kabirov, R. R.; Kireeva, N. A.; Kabirov, T. R.; Dubovik, I. Ye.; Yakupova, A. B.; Safiullina, L. M.

2012-02-01

A complex index characterizing the biological activity of soils (BAS) is suggested. It is based on an estimate of the level of activity of catalase; the number of heterotrophic and hydrocarbon oxidizing microorganisms, microscopic fungi, algae, and cyanobacteria; and the degree of development of higher plants and insects in the studied soil. The data on using the BAS coefficient for evaluating the efficiency of rehabilitation measures for oil-polluted soils are given. Such measures included introducing the following biological preparations: Lenoil based on a natural consortium of microorganisms Bacillus brevis and Arthrobacter sp.; the Azolen biofertilizer with complex action based on Azotobacter vinelandii; the Belvitamil biopreparation, which is the active silt of pulp and paper production; and a ready-mixed industrial association of aerobic and anaerobic microorganisms that contains hydrocarbon oxidizing microorganisms of the Arthrobacter, Bacillus, Candida, Desulfovibrio, and Pseudomonas genera.

Radiometric microbiologic assay for the biologically active forms of niacin

Energy Technology Data Exchange (ETDEWEB)

Kertcher, J.A.; Guilarte, T.R.; Chen, M.F.; Rider, A.A.; McIntyre, P.A.

1979-05-01

A radiometric microbiologic assay has been developed for the determination of niacin in biologic fluids. Lactobacillus plantarum produced /sup 14/CO/sub 2/ from L-(U-/sup 14/C) malic acid in quantities proportional to the amount of niacin present. The assay is specific for the biologically active forms of niacin in humans. Thirty normal hemolysates were analyzed and the values ranged from 13.0 to 17.8 ..mu..g niacin/ml RBC (mean = 15.27 +- 1.33 s.d.). Good recovery and reproducibility studies were obtained with this assay. On thirty blood samples, correlation was excellent between the radiometric and the conventional turbidimetric assays.

Physical Activity: A Tool for Improving Health (Part 1--Biological Health Benefits)

Science.gov (United States)

Gallaway, Patrick J.; Hongu, Nobuko

2015-01-01

Extension educators have been promoting and incorporating physical activities into their community-based programs and improving the health of individuals, particularly those with limited resources. This article is the first of a three-part series describing the benefits of physical activity for human health: 1) biological health benefits of…

Cell-Selective Biological Activity of Rhodium Metalloinsertors Correlates with Subcellular Localization

Science.gov (United States)

Komor, Alexis C.; Schneider, Curtis J.; Weidmann, Alyson G.; Barton, Jacqueline K.

2013-01-01

Deficiencies in the mismatch repair (MMR) pathway are associated with several types of cancers, as well as resistance to commonly used chemotherapeutics. Rhodium metalloinsertors have been found to bind DNA mismatches with high affinity and specificity in vitro, and also exhibit cell-selective cytotoxicity, targeting MMR-deficient cells over MMR-proficient cells. Ten distinct metalloinsertors with varying lipophilicities have been synthesized and their mismatch binding affinities and biological activities determined. Although DNA photocleavage experiments demonstrate that their binding affinities are quite similar, their cell-selective antiproliferative and cytotoxic activities vary significantly. Inductively coupled plasma mass spectrometry (ICP-MS) experiments have uncovered a relationship between the subcellular distribution of these metalloinsertors and their biological activities. Specifically, we find that all of our metalloinsertors localize in the nucleus at sufficient concentrations for binding to DNA mismatches. However, the metalloinsertors with high rhodium localization in the mitochondria show toxicity that is not selective for MMR-deficient cells, whereas metalloinsertors with less mitochondrial rhodium show activity that is highly selective for MMR-deficient versus proficient cells. This work supports the notion that specific targeting of the metalloinsertors to nuclear DNA gives rise to their cell-selective cytotoxic and antiproliferative activities. The selectivity in cellular targeting depends upon binding to mismatches in genomic DNA. PMID:23137296

Biochemical studies on certain biologically active nitrogenous compounds

International Nuclear Information System (INIS)

Abdel kader, S.M.; El Sayed, M.M.; El Malt, E.A.; Shaker, E.S.; Abdel Aziz, H.G.

2010-01-01

Certain biologically active nitrogenous compounds such as alkaloids are widely distributed in many wild and medicinal plants such as peganum harmala L. (Phycophyllaceae). However, less literature cited on the natural compounds was extracted from the aerial parts of this plant; therefore this study was conducted on harmal leaves using several solvents. Data indicated that methanol extract was the inhibitoriest effect against some pathogenic bacteria, particularly Streptococcus pyogenus. Chromatographic separation illustrated that presence of four compounds; the most active one was the third compound (3). Elementary analysis (C, H, N) revealed that the primary chemical structure of the active antibacterial compound (C3) was: C17 H21 N3 O7 S with molecular weight 411. Spectroscopic analysis proved that coninical structure was = 1- thioformyl, 8?- D glucoperanoside- Bis- 2, 3 dihydroisopyridino pyrrol. This new compound is represented as a noval ?- carboline alkaloid compound

PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance.

Science.gov (United States)

van Oers, Johanna M M; Roa, Sergio; Werling, Uwe; Liu, Yiyong; Genschel, Jochen; Hou, Harry; Sellers, Rani S; Modrich, Paul; Scharff, Matthew D; Edelmann, Winfried

2010-07-27

The DNA mismatch repair protein PMS2 was recently found to encode a novel endonuclease activity. To determine the biological functions of this activity in mammals, we generated endonuclease-deficient Pms2E702K knock-in mice. Pms2EK/EK mice displayed increased genomic mutation rates and a strong cancer predisposition. In addition, class switch recombination, but not somatic hypermutation, was impaired in Pms2EK/EK B cells, indicating a specific role in Ig diversity. In contrast to Pms2-/- mice, Pms2EK/EK male mice were fertile, indicating that this activity is dispensable in spermatogenesis. Therefore, the PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance and tumor suppression.

A Review of the Composition of the Essential Oils and Biological Activities of Angelica Species

Directory of Open Access Journals (Sweden)

Kandasamy Sowndhararajan

2017-09-01

Full Text Available A number of Angelica species have been used in traditional systems of medicine to treat many ailments. Especially, essential oils (EOs from the Angelica species have been used for the treatment of various health problems, including malaria, gynecological diseases, fever, anemia, and arthritis. EOs are complex mixtures of low molecular weight compounds, especially terpenoids and their oxygenated compounds. These components deliver specific fragrance and biological properties to essential oils. In this review, we summarized the chemical composition and biological activities of EOs from different species of Angelica. For this purpose, a literature search was carried out to obtain information about the EOs of Angelica species and their bioactivities from electronic databases such as PubMed, Science Direct, Wiley, Springer, ACS, Google, and other journal publications. There has been a lot of variation in the EO composition among different Angelica species. EOs from Angelica species were reported for different kinds of biological activities, such as antioxidant, anti-inflammatory, antimicrobial, immunotoxic, and insecticidal activities. The present review is an attempt to consolidate the available data for different Angelica species on the basis of major constituents in the EOs and their biological activities.

Screening of some biological activities of Alyssum fulvescens var. fulvescens known as ege madwort.

Science.gov (United States)

Ozay, Cennet; Mammadov, Ramazan

2017-09-01

In this research, the phenolic composition, antioxidant, antibacterial and cytotoxic activities of the methanolic extracts obtained from Alyssum fulvescens var. fulvescens aerial parts known as Ege kuduzotu in western Turkey, were firstly investigated. The antioxidant activity of the extract was determined by DPPH, metal chelating, phosphomolybdenum, β-carotene/linoleic acid and ferric reducing power assays. Moreover, total phenolic and flavonoid contents in the extract were investigated. The brine shrimp (Artemia salina L.) lethality test was used to investigate for the possible cytotoxic activity of the extract. Microdilution broth method was used to study antibacterial potency of extract against Gram-positive and Gram-negative bacteria. The extract exhibited good biological activities. Total phenolic and flavonoid contents in the extract were significantly correlated with antioxidant potentials. HPLC analysis showed that chlorogenic acid was the major phenolic in extract tested. The results indicated that the extract of A. fulvescens var. fulvescens may be considered as a potential source of biological agents and in vivo investigations are needed to test the biological effects of A. fulvescens var. fulvescens.

Biological activity of common mullein, a medicinal plant.

Science.gov (United States)

Turker, Arzu Ucar; Camper, N D

2002-10-01

Common Mullein (Verbascum thapsus L., Scrophulariaceae) is a medicinal plant that has been used for the treatment of inflammatory diseases, asthma, spasmodic coughs, diarrhea and other pulmonary problems. The objective of this study was to assess the biological activity of Common Mullein extracts and commercial Mullein products using selected bench top bioassays, including antibacterial, antitumor, and two toxicity assays--brine shrimp and radish seed. Extracts were prepared in water, ethanol and methanol. Antibacterial activity (especially the water extract) was observed with Klebsiella pneumonia, Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli. Agrobacterium tumefaciens-induced tumors in potato disc tissue were inhibited by all extracts. Toxicity to Brine Shrimp and to radish seed germination and growth was observed at higher concentrations of the extracts.

Synthesis and biological activity of imidazopyridine anticoccidial agents: part I.

Science.gov (United States)

Scribner, Andrew; Dennis, Richard; Hong, Jean; Lee, Shuliang; McIntyre, Donald; Perrey, David; Feng, Dennis; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

2007-01-01

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we present the synthesis and biological activity of imidazo[1,2-a]pyridine anticoccidial agents. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat Part 2: Effects on reproductive parameters, on sex behavior, on memory retention and on hypothalamic expression of aromatase and 5alpha-reductases in the offspring.

Science.gov (United States)

Colciago, A; Casati, L; Mornati, O; Vergoni, A V; Santagostino, A; Celotti, F; Negri-Cesi, P

2009-08-15

The gender-specific expression pattern of aromatase and 5alpha-reductases (5alpha-R) during brain development provides neurons the right amount of estradiol and DHT to induce a dimorphic organization of the structure. Polychlorinated biphenyls (PCBs) are endocrine disruptive pollutants; exposure to PCBs through placental transfer and breast-feeding may adversely affect the organizational action of sex steroid, resulting in long-term alteration of reproductive neuroendocrinology. The study was aimed at: a) evaluating the hypothalamic expression of aromatase, 5alpha-R1 and 5alpha-R2 in fetuses (GD20), infant (PN12), weaning (PN21) and young adult (PN60) male and female rats exposed to PCBs during development; b) correlating these parameters with the time of testicular descent, puberty onset, estrous cyclicity and copulatory behavior; c) evaluating possible alterations of some non reproductive behaviors (locomotion, learning and memory, depression/anxiety behavior). A reconstituted mixture of four indicator congeners (PCB 126, 138, 153 and 180) was injected subcutaneously to dams at the dose of 10 mg/kg daily from GD15 to GD19 and then twice a week till weanling. The results indicated that developmental PCB exposure produced important changes in the dimorphic hypothalamic expression of both aromatase and the 5alpha-Rs, which were still evident in adult animals. We observed that female puberty onset occurs earlier than in control animals without cycle irregularity, while testicular descent in males was delayed. A slight but significant impairment of sexual behavior and an important alteration in memory retention were also noted specifically in males. We conclude that PCBs might affect the dimorphic neuroendocrine control of reproductive system and of other neurobiological processes.

Biological activities of species in the genus Tulbaghia : A review ...

African Journals Online (AJOL)

Species of the genus Tulbaghia has been widely used in traditional medicine to treat various ailments such rheumatism, fits, fever, earache, tuberculosis etc. It is believed that the species possess several therapeutic properties. This paper evaluates some of the biological activities of the genus Tulbaghia. It is evident from ...

Instrumental neutron activation analysis for the certification of biological reference materials

International Nuclear Information System (INIS)

Ambulkar, M.N.; Chutke, N.L.; Garg, A.N.

1992-01-01

A multielemental instrumental neutron activation analysis (INAA) method by short and long irradiation has been employed for the determination of 22 minor and trace constituents in two proposed Standard Reference Materials P-RBF and P-WBF from Institute of Radioecology and Applied Nuclear Techniques, Czechoslovakia. Also some biological standards such as Bowen's Kale, Cabbage leaves (Poland) including wheat and rice flour samples of local origin were analysed. It is suggested that INAA is an ideal method for the certification of reference materials of biological matrices. (author). 7 refs., 1 tab

Biological Activity Predictions and Hydrogen Bonding Analysis in Quinolines

Science.gov (United States)

Gupta, Palvi; Kamni

The paper has been designed to make a comprehensive review of a particular series of organic molecular assembly in the form of compendium. An overview of general description of fifteen quinoline derivatives has been given. The biological activity spectra of quinoline derivatives have been correlated on structure activity relationships base which provides the different Pa (possibility of activity) and Pi (possibility of inactivity) values. Expositions of the role of intermolecular interactions in the identified derivatives have been discussed with the standard distance and angle cut-off criteria criteria as proposed by Desiraju and Steiner (1999) in an International monogram on crystallography. Distance-angle scatter plots for intermolecular interactions are presented for a better understanding of the packing interactions which exist in quinoline derivatives.

Application of Biologically Activated Brown Coal in Cu(II Sorption

Directory of Open Access Journals (Sweden)

Andrea Beňová

2004-12-01

Full Text Available The removal of heavy metal ions from wastewaters using different adsorbents is currently of great interest. Adsorption of cooper ions from aqueous solutions on biologically activated brown coal was investigated. Four families of adsorbents were prepared from brown coal by microorganisms activity. There were used soi microfungi such as Aspergillus niger, Aspergillus clavatus, Penicillium glabrum and Trichoderma viride. The equilibrium of the adsorption process was well described by the Langmuir isotherm and the maximum capacity of the sorbents was determined.

Brain aromatase and circulating corticosterone are rapidly regulated by combined acute stress and sexual interaction in a sex-specific manner.

Science.gov (United States)

Dickens, M J; Balthazart, J; Cornil, C A

2012-10-01

Neural production of 17β-oestradiol via aromatisation of testosterone may play a critical role in rapid, nongenomic regulation of physiological and behavioural processes. In brain nuclei implicated in the control of sexual behaviour, sexual or stressfull stimuli induce, respectively, a rapid inhibition or increase in preoptic aromatase activity (AA). In the present study, we tested quail that were either nonstressed or acutely stressed (15 min of restraint) immediately before sexual interaction (5 min) with stressed or nonstressed partners. We measured nuclei-specific AA changes, corresponding behavioural output, fertilisation rates and corticosterone (CORT) concentrations. In males, sexual interaction rapidly reversed stress-induced increases of AA in the medial preoptic nucleus (POM). This time scale (sexual stimuli on POM AA may actively preserve sexual behaviour despite stress exposure. We also found distinct sex differences in contextual physiological responses: males did not show any effect of partner status, whereas females responded to both their stress exposure and the male partner's stress exposure at the level of circulating CORT and AA. In addition, fertilisation rates and female CORT correlated with the male partner's exhibition of sexually aggressive behaviour, suggesting that female perception of the male can affect their physiology as much as direct stress. Overall, male reproduction appears relatively simple: sexual stimuli, irrespective of stress, drives major neural changes including rapid reversal of stress-induced changes of AA. By contrast, female reproduction appears more nuanced and context specific, with subjects responding physiologically and behaviourally to stress, the male partner's stress exposure, and female-directed male behaviour. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

Brain aromatase and circulating corticosterone are rapidly regulated by combined acute stress and sexual interaction in a sex specific manner

Science.gov (United States)

Dickens, M.J.; Balthazart, J.; Cornil, C. A.

2012-01-01

Neural production of 17β-oestradiol via aromatisation of testosterone may play a critical role in rapid, non-genomic regulation of physiological and behavioural processes. In brain nuclei implicated in the control of sexual behaviour, sexual or stressfull stimuli induce respectively a rapid inhibition or increase in preoptic aromatase activity (AA). Here, we tested quail that were either non-stressed or acutely stressed (15 min restraint) immediately prior to sexual interaction (5 min) with stressed or non-stressed partners. We measured nuclei-specific AA changes, corresponding behavioural output, fertilisation rates and corticosterone (CORT) concentrations. In males, sexual interaction rapidly reversed stress-induced increases of AA in the medial preoptic nucleus (POM). This time scale (behaviour suggesting that the input from the sexual stimuli on POM AA may actively preserve sexual behaviour despite stress exposure. We also found distinct sex differences in contextual physiological responses: while males did not show any effect of partner status, females responded to both their stress exposure and the male partner’s stress exposure at the level of circulating CORT and AA. In addition, fertilisation rates and female CORT correlated with the male partner’s exhibition of sexually aggressive behaviour suggesting that female perception of the male can affect their physiology as much as direct stress. Overall, male reproduction appears relatively simple – sexual stimuli, irrespective of stress, drives major neural changes including rapid reversal of stress-induced changes of AA. In contrast, female reproduction appears more nuanced and context specific, with subjects responding physiologically and behaviourally to stress, the male partner’s stress exposure, and female-directed male behaviour. PMID:22612582

Biological activities of red propolis: a rewiew

Science.gov (United States)

de Figueiredo, Sonia M; de Freitas, Marcia Christina Dornelas; de Oliveira, Daiana Teixeira; de Miranda, Marina Barcelos; Vieira-Filho, Sidney Augusto; Caligiorne, Rachel Basques

2018-02-23

• Background: The red propolis (RdProp) is a resin produced by Apis mellifera bees, which collect the reddish exudate on the surface of its botanic source, the species Dalbergiae castophyllum, popularly known in Brazil as "rabo de bugio". Considered as the 13th type of Brazilian propolis, this resin has been gaining prominence due to its natural composition, rich in bioactive substances not found in other types of propolis. • Objective: This review aims to address the most important characteristics of PV, its botanical origin, the main constituents, its biological properties and the patents related to this natural product. • Method: By means of the SciFinder, Google Patents, Patus® and Spacenet, scientific articles and patents involving the term "red propolis" were searched until August 2017 • Results: A number of biological properties, including antimicrobial, anti-inflammatory, antiparasitic, antitumor, antioxidant, metabolic and nutraceutical activities are attributed to RdProp, demonstrating the great potential of its use in the food, pharmaceutical and cosmetics industries. • Conclusion: The available papers are associated to pharmacological potential of RdProp, but the molecular mechanisms or bioactive compounds responsible for each activity have not yet been fully elucidated. The RdProp patents currently found are directed to components for the pharmaceutical industry (EP2070543A1; WO2014186851A1; FR3006589A1; CN1775277A; CN105797149A; CN1879859A), cosmetic (JP6012138B2; JP2008247830A; JP6012138B2) and food (JP5478392B2; CN101380052A; WO2006038690A1). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Aromatase inhibitors for prevention of breast cancer in postmenopausal women: a narrative review.

Science.gov (United States)

Behan, Lucy Ann; Amir, Eitan; Casper, Robert F

2015-03-01

The increasing incidence of breast cancer (BC) worldwide has resulted in widespread interest in primary prevention therapies. A number of large randomized trials have shown that selective estrogen receptor modulators can reduce the relative risk for BC by 30% to 40% in high-risk women. In early-stage BC, aromatase inhibitors (AIs) showed a 35% relative reduction in the risk of contralateral BCs compared with tamoxifen. In this narrative review, we discuss the role of AIs in the primary prevention of BC and novel research on combination hormone therapy-medical therapy for the primary prevention of BC. Using PubMed/Medline, we comprehensively searched for studies of BC primary prevention using AIs, including studies of novel methods of prevention using combination hormone therapy-BC prevention. Two large multicenter, prospective, randomized, placebo-controlled trials have evaluated AIs--anastrozole (International Breast Cancer Intervention Study II) and exemestane (Mammary Prevention 3)--for BC risk reduction in women at increased risk for BC, which we summarize. We identified five studies (three completed and two ongoing) of combination AI-hormone therapy that are undergoing investigation for BC risk reduction. AIs are effective at BC risk reduction, although long-term follow-up data are required to assess whether this risk reduction will result in reduced mortality. Combination hormone therapy-AI for BC risk reduction is experimental and warrants further investigation.

Biological Activity Assessment in Mexican Tropical Soils with Different Hydrocarbon Contamination Histories

OpenAIRE

Riveroll-Larios, Jessica; Escalante-Espinosa, Erika; Fócil-Monterrubio, Reyna L.; Díaz-Ramírez, Ildefonso J.

2015-01-01

The use of soil health indicators linked to microbial activities, such as key enzymes and respirometric profiles, helps assess the natural attenuation potential of soils contaminated with hydrocarbons. In this study, the intrinsic physicochemical characteristics, biological activity and biodegradation potential were recorded for two soils with different contamination histories (>5 years and

In vitro–in vivo correlations for endocrine activity of a mixture of 5 currently used pesticides

DEFF Research Database (Denmark)

Taxvig, Camilla; Hadrup, Niels; Boberg, Julie

2013-01-01

, indicating increased aromatase activity. The pesticide-mixtures were also investigated in vivo in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses. All 5 pesticides could be detected in the amniotic fluid, demonstrating exposure of the fetuses. Decreased estradiol...... with steroidogenesis, and it is suggested that one underlying mechanism for these pesticides is disturbance of steroidogenic enzymes....

Exploiting biological activities of brown seaweed Ecklonia cava for potential industrial applications: a review.

Science.gov (United States)

Wijesinghe, W A J P; Jeon, You-Jin

2012-03-01

Seaweeds are rich in vitamins, minerals, dietary fibres, proteins, polysaccharides and various functional polyphenols. Many researchers have focused on brown algae as a potential source of bioactive materials in the past few decades. Ecklonia cava is a brown seaweed that is abundant in the subtidal regions of Jeju Island in the Republic of Korea. This seaweed attracted extensive interest due to its multiple biological activities. E. cava has been identified as a potential producer of wide spectrum of natural substances such as carotenoids, fucoidans and phlorotannins showing different biological activities in vital industrial applications including pharmaceutical, nutraceutical, cosmeceutical and functional food. This review focuses on biological activities of the brown seaweed E. cava based on latest research results, including antioxidant, anticoagulative, antimicrobial, antihuman immunodeficiency virus, anti-inflammatory, immunomodulatory, antimutagenic, antitumour and anticancer effects. The facts summarized here may provide novel insights into the functions of E. cava and its derivatives and potentially enable their use as functional ingredients in potential industrial applications.

Eurotium (Aspergillus) repens metabolites and their biological activity.

Science.gov (United States)

Podojil, M; Sedmera, P; Vokoun, J; Betina, V; Baráthová, H; Duracková, Z; Horáková, K; Nemec, P

1978-01-01

Eurotium repens mycelium cultivated under static conditions was used to isolate and identify metabolities--echinulin, physcion, erythroglaucin, flavoglaucin and asperentin; the filtrate of the culture yielded asperentin 8-methylether. The broadest biological activity spectrum was displayed by asperentin which had antibacterial and antifungal effects and, at a concentration of 86 microgram/ml, caused 50% mor7 tality in Artemia saline larvae. The highest cytotoxicity towards HeLa cells was found in physcion which caused 50% growth inhibition at a concentration of 0.1 microgram/ml.

Synthesis, crystal structure and biological activity of novel diester cyclophanes

International Nuclear Information System (INIS)

Zhang, Pengfei; Yang, Bingqin; Fang, Xianwen; Cheng, Zhao; Yang, Meipan

2012-01-01

A series of novel diester cyclophanes was synthesized by esterification of 1,2-benzenedicarbonyl chloride with eight different diols under high dilution conditions. The structures of the compounds were verified by elemental analysis, 1 H nuclear magnetic resonance (NMR), IR spectroscopy and high resolution mass spectrometry (HRMS). The crystal structures of two compounds were characterized by single crystal X-ray diffractometry (XRD). All the new cyclophanes were evaluated for biological activities and the results showed that some of these compounds have low antibacterial or antifungal activities (author)

Adsorption of Heavy Metals on Biologically Activated Brown Coal Sludge

Directory of Open Access Journals (Sweden)

Mária Praščáková

2005-11-01

Full Text Available Adsorption of cooper (II and zinc (II ions from aqueous solutions on a biologically activated brown coal sludge was investigated. Four families of adsorbents were prepared from the brown coal sludge bya microorganism’s activity. There were used microscopic fungi such as Aspergillus niger, Aspergillus clavatus, Penicillium glabrum and Trichoderma viride. Prepared sorbents were capable of removing Cu (II and Zn (II. The sorption isotherm has been constructed and the specific metal uptake and the maximum capacity of the adsorbent have been determined.

Screening vaccine formulations for biological activity using fresh human whole blood.

OpenAIRE

Brookes, RH; Hakimi, J; Ha, Y; Aboutorabian, S; Ausar, SF; Hasija, M; Smith, SG; Todryk, SM; Dockrell, HM; Rahman, N

2014-01-01

Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it rem...

Mineralogical characteristics of the silica polymorphs in relation to their biological activities

Energy Technology Data Exchange (ETDEWEB)

Guthrie, G.D. Jr. [Los Alamos National Lab., NM (United States); Heaney, P.J. [Princeton Univ., NJ (United States). Dept. of Geological and Geophysical Sciences

1993-10-01

Numerous aspects of minerals (including the silica polymorphs) can effect their biological activities. These include periodic structures, compositional variations, dissolution characteristics, surface properties, and particle size/shape. In order to understand mineral-induced pathogenesis in a mechanistic way, the links between these properties and biochemical processes must be elucidated. This paper presents some of the basic properties of the silica polymorphs that may relate to pathogenicity and mineralogical strategies for designing biological assays to evaluate these properties.

Phytochemistry and biological activities of Heracleum persicum: a review.

Science.gov (United States)

Majidi, Zahra; Sadati Lamardi, S N

2018-05-24

Heracleum persicum Desf. ex Fisch is used in Iranian traditional medicines, for the treatment of various diseases including neurological, gastrointestinal, respiratory, rheumatological and urinary tract diseases. In phytochemical analysis of H. persicum, several classes of natural chemicals including volatile (aliphatic esters, carbonyls, phenyl propenes and terpenes) and nonvolatile (flavonoids, furanocoumarins, tannins and alkaloids) constituents as well as different minerals have been identified. Scientific studies on H. persicum proved that it has a wide range of biological and pharmacological activities. This article has provided comprehensive information on Iranian traditional uses, phytochemistry and pharmacological activities of H. persicum. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Diversity and Biological Activities of Endophytic Fungi Associated with Micropropagated Medicinal Plant Echinacea purpurea (L.) Moench

Science.gov (United States)

2012-08-01

1105 Diversity and Biological Activities of Endophytic Fungi Associated with Micropropagated Medicinal Plant Echinacea purpurea (L.) Moench Luiz H...fungal community and micropropagated clones of E. purpurea was re-established after acclimatization to soil and the endophytic fungi produced compounds...Diversity and Biological Activities of Endophytic Fungi Associated with Micropropagated Medicinal Plant Echinacea purpurea (L.) Moench 5a. CONTRACT

Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics

International Nuclear Information System (INIS)

Kandhasamy, Subramani; Ramanathan, Giriprasath; Muthukumar, Thangavelu; Thyagarajan, SitaLakshmi; Umamaheshwari, Narayanan; Santhanakrishnan, V P; Sivagnanam, Uma Tiruchirapalli; Perumal, Paramasivan Thirumalai

2017-01-01

The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a–5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: (1T46)) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48 h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the

Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics

Energy Technology Data Exchange (ETDEWEB)

Kandhasamy, Subramani [Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu (India); Ramanathan, Giriprasath [Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu (India); Muthukumar, Thangavelu [Department of Clinical and Experimental Medicine (IKE), Division of Neuro and Inflammation Sciences (NIV), Linkoping University (Sweden); Thyagarajan, SitaLakshmi [Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu (India); Umamaheshwari, Narayanan [Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu (India); Santhanakrishnan, V P [Department of Plant Biotechnology, TNAU, Coimbatore, Tamilnadu (India); Sivagnanam, Uma Tiruchirapalli, E-mail: suma67@gmail.com [Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu (India); Perumal, Paramasivan Thirumalai, E-mail: ptperumal@gmail.com [Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu (India)

2017-05-01

The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a–5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: (1T46)) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48 h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the

Ecological Roles and Biological Activities of Specialized Metabolites from the Genus Nicotiana.

Science.gov (United States)

Jassbi, Amir Reza; Zare, Somayeh; Asadollahi, Mojtaba; Schuman, Meredith C

2017-10-11

Species of Nicotiana grow naturally in different parts of the world and have long been used both medicinally and recreationally by human societies. More recently in our history, Nicotiana tabacum has attracted interest as one of the most economically important industrial crops. Nicotiana species are frequently investigated for their bioactive natural products, and the ecological role of their specialized metabolites in responses to abiotic stress or biotic stress factors like pathogens and herbivores. The interest of tobacco companies in genetic information as well as the success of a few wild tobacco species as experimental model organisms have resulted in growing knowledge about the molecular biology and ecology of these plants and functional studies of the plant's natural products. Although a large number of reviews and books on biologically active natural products already exists, mostly from N. tabacum, we focus our attention on the ecological roles and biological activity of natural products, versus products from cured and processed material, in this Review. The studied compounds include alkaloids, aromatic compounds, flavonoids, volatiles, sesquiterpenoids, diterpenes alcohols, and sugar esters from trichomes of the plants, and recently characterized acyclic hydroxygeranyllinalool diterpene glycosides (HGL-DTGs). In this Review (1800s-2017), we describe the above-mentioned classes of natural products, emphasizing their biological activities and functions as they have been determined either in bioassay-guided purification approaches or in bioassays with plants in which the expression of specific biosynthetic genes has been genetically manipulated. Additionally, a review on the history, taxonomy, ecology, and medicinal application of different Nicotiana species growing around the globe presented in this Review may be of interest for pharmacognosists, natural products, and ecological chemists.

Supercritical Algal Extracts: A Source of Biologically Active Compounds from Nature

Directory of Open Access Journals (Sweden)

Izabela Michalak

2015-01-01

Full Text Available The paper discusses the potential applicability of the process of supercritical fluid extraction (SFE in the production of algal extracts with the consideration of the process conditions and yields. State of the art in the research on solvent-free isolation of biologically active compounds from the biomass of algae was presented. Various aspects related with the properties of useful compounds found in cells of microalgae and macroalgae were discussed, including their potential applications as the natural components of plant protection products (biostimulants and bioregulators, dietary feed and food supplements, and pharmaceuticals. Analytical methods of determination of the natural compounds derived from algae were discussed. Algal extracts produced by SFE process enable obtaining a solvent-free concentrate of biologically active compounds; however, detailed economic analysis, as well as elaboration of products standardization procedures, is required in order to implement the products in the market.

On the possibility of biologically active fenole substances forming during irradiation of vegetable origin products

International Nuclear Information System (INIS)

Koval'skaya, L.P.; Petrash, I.P.; Medvedeva, T.N.; Lezhneva, M.L.; Shchegoleva, G.I.

1974-01-01

The purpose of this study was to find out whether biologically active substances of phenol nature can form upon irradiation of fresh fruits and vegetables with doses of 200-300 Krad, to ascertain the stability of these substances during storage and processing, and to see whether they display cytostatic effects. The results of the study led to modifications and improvements in the methods used to study biologically active substances of phenol nature in fresh fruits irradiated with 200-300 krad. The total amount of phenolic compounds was found to be somewhat increased upon their extraction with cold ethanol. Of the substances detected in extracts from red tomatoes, the contens of chlorogenic acid, caffeic acid, and naranguenine were appreciably increased. Neither chemical methods nor bioassays revealed in irradiated juices and fruits any biologically active substances affecting the living organism. (E.T.)

Influence of Technological Processes on Biologically Active Compounds of Produced Grapes Juices

Czech Academy of Sciences Publication Activity Database

Tříska, Jan; Balík, J.; Strohalm, J.; Novotná, P.; Vrchotová, Naděžda; Lefnerová, D.; Landfeld, A.; Híc, P.; Tománková, E.; Veverka, J.; Houška, M.

2016-01-01

Roč. 9, č. 3 (2016), s. 421-429 ISSN 1935-5130 R&D Projects: GA MŠk(CZ) LO1415; GA MZe QJ1210258; GA MZe QI91B094 Institutional support: RVO:67179843 Keywords : Grapevine juices * Thermomaceration * Biologically active compounds * Antioxidative capacity * Total polyphenols * Antimutagenic activity Subject RIV: GM - Food Processing Impact factor: 2.576, year: 2016

Determination of mercury concentration in biological materials by neutron activation analysis

International Nuclear Information System (INIS)

Munoz, L.; Gras, N.; Cortes, E.; Cassorla, V.

1983-01-01

The objective of this work was to obtain a confident analytical method for measuring the mercury concentration in biological materials. Destructive neutron activation analysis was used for this purpose and a radiochemical separation method was studied to isolate the mercury from its main interferences: sodium and phosphorus, because these elements in biological materials are in high concentrations. The method developed was based on the copper amalgamation under controlled conditions. Yield and reproductibility studies were performed using 203 Hg as radioactive tracer. Finally, food samples of regular consumption were analyzed and the results were compared with those recommended by FAO/WHO. (Author)

CYP19A1 polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial

DEFF Research Database (Denmark)

Leyland-Jones, Brian; Gray, Kathryn P; Abramovitz, Mark

2015-01-01

To determine whether CYP19A1 polymorphisms are associated with abnormal activity of aromatase and with musculoskeletal and bone side effects of aromatase inhibitors. DNA was isolated from tumor specimens of 4861 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1...

Neutron-Activation Analysis of Biological Material with High Radiation Levels

Energy Technology Data Exchange (ETDEWEB)

Samsahl, K

1966-09-15

A method has been developed for the chemical separation and subsequent gamma-spectrometric analysis of the alkali metals, the alkaline earths, the rare earths, chromium, hafnium, lanthanum, manganese, phosphorus, scandium and silver in neutron-activated biological material. The separation steps, being fully automatic, are based on a combination of ion-exchange and partition chromatography and require 40 min.

Neutron-Activation Analysis of Biological Material with High Radiation Levels

International Nuclear Information System (INIS)

Samsahl, K.

1966-09-01

A method has been developed for the chemical separation and subsequent gamma-spectrometric analysis of the alkali metals, the alkaline earths, the rare earths, chromium, hafnium, lanthanum, manganese, phosphorus, scandium and silver in neutron-activated biological material. The separation steps, being fully automatic, are based on a combination of ion-exchange and partition chromatography and require 40 min

Synthesis, crystal structure and biological activity of novel diester cyclophanes

Energy Technology Data Exchange (ETDEWEB)

Zhang, Pengfei; Yang, Bingqin; Fang, Xianwen; Cheng, Zhao; Yang, Meipan, E-mail: yangbq@nwu.edu.cn [Department of Chemistry, Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, Northwest University, Shaanxi (China)

2012-10-15

A series of novel diester cyclophanes was synthesized by esterification of 1,2-benzenedicarbonyl chloride with eight different diols under high dilution conditions. The structures of the compounds were verified by elemental analysis, {sup 1}H nuclear magnetic resonance (NMR), IR spectroscopy and high resolution mass spectrometry (HRMS). The crystal structures of two compounds were characterized by single crystal X-ray diffractometry (XRD). All the new cyclophanes were evaluated for biological activities and the results showed that some of these compounds have low antibacterial or antifungal activities (author)

Evidence for the prevention of bone loss in elderly and old early non-metastatic breast cancer patients treated with aromatase inhibitors

DEFF Research Database (Denmark)

Gunmalm, V.; Jørgensen, N. R.; Abrahamsen, B.

2017-01-01

Breast cancer (BC) is the most common cancer amongst women worldwide. Bone health is emerging as an important issue for BC survivors. In this literature study, we focus on agents for preventing bone loss in early non-metastatic estrogen receptor positive BC in treatment with aromatase inhibitors...... (AI) and to assess the evidence for antiresorptive treatment of bone loss in early non-metastatic breast cancer. We included randomized controlled trials (RCT's) comparing: (a) bisphosphonates and control; (b) different bisphosphonates; (c) denosumab and control and (d) bisphosphonates vs. denosumab...... in early non-metastatic BC women in AI treatment. Among antiresorptives, zoledronic acid currently has the highest evidence for prevention of AI associated bone loss in early non-metastatic BC. Data on fracture prevention among all patients, elderly and old is sparse. More randomized controlled studies...

NBS activities in biological reference materials

Energy Technology Data Exchange (ETDEWEB)

Rasberry, S.D.

1988-12-01

NBS activities in biological reference materials during 1986-1988 are described with a preview of plans for future certifications of reference materials. During the period, work has been completed or partially completed on about 40 reference materials of importance to health, nutrition, and environmental quality. Some of the reference materials that have been completed during the period and are described include: creatinine (SRM 914a), bovine serum albumin (SRM 927a), cholesterol in human serum (SRM's 1951-1952), aspartate aminotransferase (RM 8430), cholesterol and fat-soluble vitamins in coconut oil (SRM 1563), wheat flour (SRM 1567a), rice flour (SRM 1568a), mixed diet (RM 8431a), dinitropyrene isomers and 1-nitropyrene (SRM 1596), and complex PAH's from coal tar (SRM 1597). Oyster tissue (SRM 1566a) is being analyzed and should be available in 1988.

Optically and biologically active mussel protein-coated double-walled carbon nanotubes.

Science.gov (United States)

Jung, Yong Chae; Muramatsu, Hiroyuki; Fujisawa, Kazunori; Kim, Jin Hee; Hayashi, Takuya; Kim, Yoong Ahm; Endo, Morinobu; Terrones, Mauricio; Dresselhaus, Mildred S

2011-12-02

A method of dispersing strongly bundled double-walled carbon nanotubes (DWNTs) via a homogeneous coating of mussel protein in an aqueous solution is presented. Optical activity, mechanical strength, as well as electrical conductivity coming from the nanotubes and the versatile biological activity from the mussel protein make mussel-coated DWNTs promising as a multifunctional scaffold and for anti-fouling materials. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Correlation between biological activity and electron transferring of bovine liver catalase: Osmolytes effects

International Nuclear Information System (INIS)

Tehrani, H. Sepasi; Moosavi-Movahedi, A.A.; Ghourchian, H.

2013-01-01

Highlights: • Proline increases ET in Bovine Liver Catalase (BLC) whereas histidine decreases it. • Proline also increased the biological activity, whereas histidine decreased it. • Electron transferring and biological activity for BLC are directly correlated. • Proline causes favorable ET for BLC shown by positive E 1/2 (E°′) and negative ΔG. • Histidine makes ET unfavorable for BLC, manifested by E 1/2 (E°′) 0. -- Abstract: Catalase is a crucial antioxidant enzyme that protects life against detrimental effects of H 2 O 2 by disproportionating it into water and molecular oxygen. Effect of proline as a compatible and histidine as a non compatible osmolyte on the electron transferring and midpoint potential of catalase has been investigated. Proline increases the midpoint potential (ΔE m > 0), therefore causing the ΔG ET to be less positive and making the electron transfer reaction more facile whereas histidine decreases the E m (ΔE m ET , thereby rendering the electron transfer reaction less efficient. These results indicate the inhibitory effect of histidine evident by a −37% decrease in the cathodic peak current compared to 16% increase in the case of proline indicative of activation. The insight paves the tedious way towards our ultimate goal of elucidating a correlation between biological activity and electron transferring

Use of biological activities to monitor the removal of fuel contaminants - perspective for monitoring hydrocarbon contamination: A review

CSIR Research Space (South Africa)

Maila, MP

2005-01-01

Full Text Available Soil biological activities are vital for the restoration of soil contaminated with hydrocarbons. Their role includes the biotransformation of petroleum compounds into harmless compounds. In this paper, the use of biological activities as potential...

A peptide derived from alpha-fetoprotein inhibits the proliferation induced by estradiol in mammary tumor cells in culture.

Science.gov (United States)

Sierralta, Walter D; Epuñan, Maria J; Reyes, José M; Valladares, Luis E; Andersen, Thomas T; Bennett, James A; Jacobson, Herbert I; Pino, Ana M

2008-01-01

This study was aimed to obtain additional information on the activity of a cyclized 9-amino acid peptide (cP) containing the active site of alpha fetoprotein, which inhibits the estrogen-stimulated proliferation of tumor cells in culture and of xenografts in immunodeficient mice. Breast cancer cells cultured in the presence of 2 nM estradiol were exposed to cP for different periods and their proliferation, estradiol binding parameters, clustering tendency and expression of E-cadherin and p21Cip1 were analyzed by biochemical and cell biology methods. The proliferation of MCF7 cells was significantly decreased by the addition of 2 microg/ml cP to the medium. cP did not increase cell death rate nor alter the number of binding sites for estradiol nor the endogenous aromatase activity of MCF7 cells. cP also decreased the proliferation of estrogen-dependent ZR75-1 cells but had no effect on estrogen-independent MDA-MB-231 cells. An increased nuclear p21Cip1 expression detected after cP treatment suggests that cP slows MCF7 cell proliferation via this regulator. We propose that cP could represent a novel breast cancer therapeutic agent whose mechanism of action is different from that of tamoxifen or of inhibitors of aromatase.

Predicting Adherence to Aromatase Inhibitor Therapy among Breast Cancer Survivors: An Application of the Protection Motivation Theory

Directory of Open Access Journals (Sweden)

Monita Karmakar MS

2017-02-01

Full Text Available The purpose of this observational study was to determine if the Protection Motivation Theory could predict and explain adherence to aromatase inhibitor (AI therapy among breast cancer survivors. Purposive sampling was used to identify 288 survivors who had been prescribed AI therapy. A valid and reliable survey was mailed to survivors. A total of 145 survivors completed the survey. The Morisky scale was used to measure adherence to AI. The survivors reported a mean score of 6.84 (±0.66 on the scale. Nearly 4 in 10 survivors (38% were non-adherent. Adherence differed by age, marital status, insurance status, income, and presence of co-morbid conditions. Self-efficacy (r=0.485, protection motivation (r=0.310, and Response Efficacy (r=0.206 were positively and significantly correlated with adherence. Response Cost (r=-0.235 was negatively correlated with adherence. The coping appraisal constructs were statistically significant predictors medication adherence (β=0.437 with self-efficacy being the strongest significant predictor of adherence (β = 0.429.

Predicting Adherence to Aromatase Inhibitor Therapy among Breast Cancer Survivors: An Application of the Protection Motivation Theory

Science.gov (United States)

Karmakar, Monita; Pinto, Sharrel L; Jordan, Timothy R; Mohamed, Iman; Holiday-Goodman, Monica

2017-01-01

The purpose of this observational study was to determine if the Protection Motivation Theory could predict and explain adherence to aromatase inhibitor (AI) therapy among breast cancer survivors. Purposive sampling was used to identify 288 survivors who had been prescribed AI therapy. A valid and reliable survey was mailed to survivors. A total of 145 survivors completed the survey. The Morisky scale was used to measure adherence to AI. The survivors reported a mean score of 6.84 (±0.66) on the scale. Nearly 4 in 10 survivors (38%) were non-adherent. Adherence differed by age, marital status, insurance status, income, and presence of co-morbid conditions. Self-efficacy (r=0.485), protection motivation (r=0.310), and Response Efficacy (r=0.206) were positively and significantly correlated with adherence. Response Cost (r=-0.235) was negatively correlated with adherence. The coping appraisal constructs were statistically significant predictors medication adherence (β=0.437) with self-efficacy being the strongest significant predictor of adherence (β = 0.429). PMID:28469437

Pharmaceutical wastewater treatment by internal micro-electrolysis--coagulation, biological treatment and activated carbon adsorption.

Science.gov (United States)

Wang, Kangle; Liu, Suiqing; Zhang, Qiang; He, Yiliang

2009-12-01

Treatment of pharmaceutical wastewater by the combined process of internal micro-electrolysis and coagulation, biological treatment and activated carbon adsorption was studied. Internal micro-electrolysis and coagulation served as the pretreatment for the wastewater before biological treatment to reduce the contaminants' toxicity to microbes and improve the biodegradability of wastewater to guarantee the smooth operation of the biological process. Biological treatment was the main body of the whole process which took an unparalleled role in removing COD (chemical oxygen demand). Activated carbon adsorption was adopted as the post-treatment process to further remove the remaining non-biodegradable particles. Results showed that the removal rates of COD and S2- (sulphide ion) by pretreatment were 66.9% and 98.9%, respectively, and the biodegradability, as measured by the ratio of biodegradable COD to initial COD, of the wastewater was greatly improved from 0.16 +/- 0.02 to 0.41 +/- 0.02. The overall removal rate of COD in the wastewater achieved by this combined treatment process was up to 96%, and the effluent COD met the Chinese tertiary discharge standard (GB 8978-1996).

Evaluation of Biologically Active Compounds from Calendula officinalis Flowers using Spectrophotometry

Directory of Open Access Journals (Sweden)

Butnariu Monica

2012-04-01

Full Text Available Abstract Background This study aimed to quantify the active biological compounds in C. officinalis flowers. Based on the active principles and biological properties of marigolds flowers reported in the literature, we sought to obtain and characterize the molecular composition of extracts prepared using different solvents. The antioxidant capacities of extracts were assessed by using spectrophotometry to measure both absorbance of the colorimetric free radical scavenger 2,2-diphenyl-1-picrylhydrazyl (DPPH as well as the total antioxidant potential, using the ferric reducing power (FRAP assay. Results Spectrophotometric assays in the ultraviolet-visible (UV-VIS region enabled identification and characterization of the full range of phenolic and flavonoids acids, and high-performance liquid chromatography (HPLC was used to identify and quantify phenolic compounds (depending on the method of extraction. Methanol ensured more efficient extraction of flavonoids than the other solvents tested. Antioxidant activity in methanolic extracts was correlated with the polyphenol content. Conclusions The UV-VIS spectra of assimilator pigments (e.g. chlorophylls, polyphenols and flavonoids extracted from the C. officinalis flowers consisted in quantitative evaluation of compounds which absorb to wavelengths broader than 360 nm.

Chemistry and Biological Activities of Flavonoids: An Overview

Directory of Open Access Journals (Sweden)

Shashank Kumar

2013-01-01

Full Text Available There has been increasing interest in the research on flavonoids from plant sources because of their versatile health benefits reported in various epidemiological studies. Since flavonoids are directly associated with human dietary ingredients and health, there is need to evaluate structure and function relationship. The bioavailability, metabolism, and biological activity of flavonoids depend upon the configuration, total number of hydroxyl groups, and substitution of functional groups about their nuclear structure. Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine. Most recent researches have focused on the health aspects of flavonoids for humans. Many flavonoids are shown to have antioxidative activity, free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, and anticancer activities, while some flavonoids exhibit potential antiviral activities. In plant systems, flavonoids help in combating oxidative stress and act as growth regulators. For pharmaceutical purposes cost-effective bulk production of different types of flavonoids has been made possible with the help of microbial biotechnology. This review highlights the structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production.

Biological Activity and Phytochemical Study of Scutellaria platystegia.

Science.gov (United States)

Madani Mousavi, Seyedeh Neda; Delazar, Abbas; Nazemiyeh, Hossein; Khodaie, Laleh

2015-01-01

This study aimed to determine biological activity and phytochemical study of Scutellaria platystegia (family Labiatae). Methanolic (MeOH) extract of aerial parts of S. platystegia and SPE fractions of methanolic extract (specially 20% and 40% methanolic fractions), growing in East-Azarbaijan province of Iran were found to have radical scavenging activity by DPPH (2, 2-diphenyl -1- pycryl hydrazyl) assay. Dichloromethane (DCM) extract of this plant exhibited animalarial activity by cell free method providing IC50 at 1.1876 mg/mL. Crude extracts did not exhibit any toxicity assessed by brine shrimp lethality assay. Phytochemical study of methanolic extract by using reverse phase HPLC method and NMR instrument for isolation and identification of pure compounds respectively, yielded 2-(4- hydroxy phenyl) ethyl-O-β-D- glucopyranoside from 10% and apigenin 7-O-glucoside, verbascoside and martynoside from 40% SPE fraction. Occurance of verbascoside and martynoside as biochemical markers appeared to be widespread in this genus. Antioxidant and antimalarial activity of MeOH and DCM extracts, respectively, as well as no general toxicity of them could provide a basis for further in-vitro and in-vivo studies and clinical trials to develop new therapeutical alternatives.

Chemistry and Biological Activities of Flavonoids: An Overview

Science.gov (United States)

Kumar, Shashank; Pandey, Abhay K.

2013-01-01

There has been increasing interest in the research on flavonoids from plant sources because of their versatile health benefits reported in various epidemiological studies. Since flavonoids are directly associated with human dietary ingredients and health, there is need to evaluate structure and function relationship. The bioavailability, metabolism, and biological activity of flavonoids depend upon the configuration, total number of hydroxyl groups, and substitution of functional groups about their nuclear structure. Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine. Most recent researches have focused on the health aspects of flavonoids for humans. Many flavonoids are shown to have antioxidative activity, free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, and anticancer activities, while some flavonoids exhibit potential antiviral activities. In plant systems, flavonoids help in combating oxidative stress and act as growth regulators. For pharmaceutical purposes cost-effective bulk production of different types of flavonoids has been made possible with the help of microbial biotechnology. This review highlights the structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production. PMID:24470791

Biological preconcentrator

Science.gov (United States)

Manginell, Ronald P [Albuquerque, NM; Bunker, Bruce C [Albuquerque, NM; Huber, Dale L [Albuquerque, NM

2008-09-09

A biological preconcentrator comprises a stimulus-responsive active film on a stimulus-producing microfabricated platform. The active film can comprise a thermally switchable polymer film that can be used to selectively absorb and desorb proteins from a protein mixture. The biological microfabricated platform can comprise a thin membrane suspended on a substrate with an integral resistive heater and/or thermoelectric cooler for thermal switching of the active polymer film disposed on the membrane. The active polymer film can comprise hydrogel-like polymers, such as poly(ethylene oxide) or poly(n-isopropylacrylamide), that are tethered to the membrane. The biological preconcentrator can be fabricated with semiconductor materials and technologies.

Synthesis and biological activity of oxytocin analogues containing unnatural amino acids in position 9: structure activity study

Czech Academy of Sciences Publication Activity Database

Magafa, V.; Borovičková, Lenka; Slaninová, Jiřina; Cordopatis, P.

2010-01-01

Roč. 38, č. 5 (2010), s. 1549-1559 ISSN 0939-4451 Institutional research plan: CEZ:AV0Z40550506 Keywords : oxytocin antagonists * position 9 * unnatural amino acids * biological activity Subject RIV: CC - Organic Chemistry Impact factor: 4.106, year: 2010

Effect of testosterone replacement on the alteration of steroid metabolism in the hypothalamic-preoptic area of male hamsters treated with melatonin.

Science.gov (United States)

Petterborg, L J; West, D A; Rudeen, P K; Ganjam, V K

1991-11-01

Adult male hamsters were maintained under 14 hours of light per day and randomly assigned to groups that received daily afternoon melatonin (25 micrograms) or vehicle injections. Animals from both groups were killed following 4, 8, and 12 weeks of treatment. By 12 weeks, the melatonin-treated hamsters had significant reductions in the weights of the testes and seminal vesicles, serum testosterone levels, and activities did not differ between groups. In a second experiment, hamsters were hypothalamic-preoptic area (HPOA) aromatase activities. Hypothalamic-preoptic area 5 alpha-reductase activities did not differ between groups. In a second experiment, hamsters were again treated with melatonin or vehicle for 12 weeks prior to being killed. After 10 weeks of treatment, groups of melatonin-treated animals received subcutaneous silastic capsules (5, 10, or 20 mm) filled with testosterone. Animals in two other groups were given blank implants or no implants at all. Two weeks later, at autopsy, reproductive organ weights, serum testosterone levels, and HPOA aromatase activities were significantly suppressed by melatonin administration. 5 alpha-Reductase activity in the HPOA was not affected. Hamsters that had been given the 10- and 20-mm testosterone implants exhibited normal seminal vesicle weights and HPOA aromatase activities. These results suggest that melatonin-induced reduction of HPOA aromatase activity is mediated by decreased circulating levels of testosterone.

Characterization and expression profile of the ovarian cytochrome P-450 aromatase (cyp19A1) gene during thermolabile sex determination in Pejerrey, Odontesthes bonariensis

Science.gov (United States)

Karube, M.; Fernandino, J.I.; Strobl-Mazzulla, P.; Strussmann, C.A.; Yoshizaki, G.; Somoza, G.M.; Patino, R.

2007-01-01

Cytochrome P450 aromatase (cyp19) is an enzyme that catalyzes the conversion of androgens to estrogens and may play a role in temperature- dependent sex determination (TSD) of reptiles, amphibians, and fishes. In this study, the ovarian P450 aromatase form (cyp19A1) of pejerrey Odontesthes bonariensis, a teleost with marked TSD, was cloned and its expression profile evaluated during gonadal differentiation at feminizing (17??C, 100% females), mixed-sex producing (24 and 25??C, 73.3 and 26.7% females, respectively), and masculinizing (29??C, 0% females) temperatures. The deduced cyp19A1 amino acid sequence shared high identity (>77.8%) with that from other teleosts but had low identity (<61.8%) with brain forms (cyp19A2), including that of pejerrey itself. The tissue distribution analysis of cyp19A1 mRNA in adult fish revealed high expression in the ovary. Semi-quantitative reverse transcription polymerase chain reaction analysis of the bodies of larvae revealed that cyp19A1 expression increased before the appearance of the first histological signs of ovarian differentiation at the feminizing temperature but remained low at the masculinizing temperature. The expression levels at mixed-sex producing temperatures were bimodal rather than intermediate, showing low and high modal values similar to those at the feminizing and masculinizing temperatures, respectively. The population percentages of high and low expression levels at intermediate temperatures were proportional to the percentage of females and males, respectively, and high levels were first observed at about the time of sex differentiation of females. These results suggest that cyp19A1 is involved in the process of ovarian formation and possibly also in the TSD of pejerrey. ?? 2007 Wiley-Liss, Inc.

Biological Activity of Tannins from Acacia mangium Bark Extracted by Different Solvents

Directory of Open Access Journals (Sweden)

E. Wina

2010-08-01

Full Text Available Acacia mangium bark is abundant byproduct of wood industry in Indonesia. It is underutilized and mainly used as fire wood for the wood industry. The bark contains high level of tannin but the tannin has not been extracted or produced commercially. Tannin isolate can be used for several purposes such as tanning agent for leather, adhesive for plywood or particle board, etc. In ruminant, tannin can be detrimental but can also be beneficial. This experiment was aimed of getting the highest yield of tannin extract with the highest biological activity in rumen fermentation. Nine different solvents at different temperatures were used to extract tannin from A. mangium bark. The extracts were analyzed for their tannin contents and biological activities. Tannin content was analyzed using folin ciocalteau and butanol-HCl methods. Biological activity was described as a percentage of an increase in gas production in the in vitro rumen-buffer fermentation, with and without addition of PEG. The results show that Na2SO3 solution extracted more tannin than other solutions and the higher the concentration of Na2SO3 solution, the higher the yield of tannin extract. The solution of 6% sodium sulphite gave the highest yield of tannin extract (31.2% of original bark sample and the highest concentration of tannin (18.26% but produced a negative effect on in vitro fermentation (% increase of gas production = 2.70%. Extraction with 50% acetone gave a high yield of extract (22.28% of original bark which contained 12.98% of tannin and showed the highest biological response (% increase of gas production = 216%. In conclusion, sodium sulphite solution is not recommended for tannin extraction if the tannin will be used as feed additive in ruminant feed; on the other hand, the aqueous acetone (50% acetone solution is a better choice to be used.

Summary of diamino pyrazoles derived and study their biological activities

International Nuclear Information System (INIS)

Hagui, Marwa

2016-01-01

The work involves the synthesis of new heterocyclic structures diamino pyrazoles derivatives that are present in many natural products and products of pharmacological and therapeutic interests and study their biological activities. In order to develop a radiotracer interest and use in diagnostic nuclear medicine, we are interested to synthesis a pyrazole derivative with the precursor [Re(CO)5Br] and studying the antibacterial and antifungal activity of 3.5-diamino pyrazole and even thioamide complex rhenium. The objectives of our workout: 1/ Synthesis of molecules 3,5-diamino pyrazole and thioamide. 2/ Synthesis of 3,5-diamino pyrazole-rhenium complex. 3/ The in vitro study: Bacteriological Tests (Study of antibacterial and antifungal activity of 3,5-diamino pyrazole and thioamide). The first part of this work concerns the chemical synthesis of molecules such as: thioamide, Amp z1 Ampz2 and then we had synthesized the complex 3,5-diamino pyrazole-rhenium. Similarly we determined the physicochemical characteristics of the compounds synthesized by CLHP, CCM and RMN ( 1 H, 13 C). The second part is devoted to the study in vitro of biological activities of the synthesized molecules and complex 3,5 diaminopyrazole-rhenium with concentration 1 mg/mL and 2 mg/mL. The results allow us to say that the thioamide and Ampz2 have antibacterial activity against S. enterica and Ampz2 has low activity against S. aureus and P. aeruginossa. Other pyrazole derivatives have no significant antibacterial and antifungal activity. The results also show that the synthesized compounds of concentration 2 mg/mL in relation to the inhibition zones of amoxicillin and DMSO: 1/ Escherichia coli, there is antibacterial activity for thioamide, and the Amp z1-Re Ampz2 compound. 2/ Staphylococcus aureus, the complex Ampz 1-Re and the thioamide have significant antibacterial activity. 3/ Salmonella, we observe that the thioamide molecules, Ampz2 and Amp z1-Re have significant antibacterial activity

Introduction to the Symposium "Leading Students and Faculty to Quantitative Biology through Active Learning".

Science.gov (United States)

Waldrop, Lindsay D; Miller, Laura A

2015-11-01

The broad aim of this symposium and set of associated papers is to motivate the use of inquiry-based, active-learning teaching techniques in undergraduate quantitative biology courses. Practical information, resources, and ready-to-use classroom exercises relevant to physicists, mathematicians, biologists, and engineers are presented. These resources can be used to address the lack of preparation of college students in STEM fields entering the workforce by providing experience working on interdisciplinary and multidisciplinary problems in mathematical biology in a group setting. Such approaches can also indirectly help attract and retain under-represented students who benefit the most from "non-traditional" learning styles and strategies, including inquiry-based, collaborative, and active learning. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Traditional Uses, Chemical Constituents, and Biological Activities of Bixa orellana L.: A Review

Directory of Open Access Journals (Sweden)

Daniela de Araújo Vilar

2014-01-01

Full Text Available Bixa orellana L., popularly known as “urucum,” has been used by indigenous communities in Brazil and other tropical countries for several biological applications, which indicates its potential use as an active ingredient in pharmaceutical products. The aim of this work was to report the main evidence found in the literature, concerning the ethnopharmacology, the biological activity, and the phytochemistry studies related to Bixa orellana L. Therefore, this work comprises a systematic review about the use of Bixa orellana in the American continent and analysis of the data collected. This study shows the well-characterized pharmacological actions that may be considered relevant for the future development of an innovative therapeutic agent.

Synthesis, Crystal Structure and Biological Activities of Novel Anthranilic(Isophthalic) Acid Esters

Institute of Scientific and Technical Information of China (English)

YAN Tao; YU Guan-ping; LIU Peng-fei; XIONG Li-xia; YU Shu-jing; LI Zheng-ming

2012-01-01

In search of environmentally benign insecticides with high activity,low toxicity and low resistance,a series of novel anthranilic(isophthalic) acid esters was designed and synthesized based on the structure of ryanodine modulating agent.All the compounds were characterized by 1H NMR spectra,elemental analysis or high resolution mass spectrometry(HRMS).The preliminary results of biological activity assessment indicate that some of the title compounds exhibit certain but unremarkable insecticidal activity against Mythimna separata Walker at 200 mg/L and fungicidal activities against five funguses at 50 mg/L.

Research and Teaching: Instructor Use of Group Active Learning in an Introductory Biology Sequence

Science.gov (United States)

Auerbach, Anna Jo; Schussler, Elisabeth E.

2016-01-01

Active learning (or learner-centered) pedagogies have been shown to enhance student learning in introductory biology courses. Student collaboration has also been shown to enhance student learning and may be a critical part of effective active learning practices. This study focused on documenting the use of individual active learning and group…

Biology Myth-Killers

Science.gov (United States)

Lampert, Evan

2014-01-01

"Biology Myth-Killers" is an activity designed to identify and correct common misconceptions for high school and college introductory biology courses. Students identify common myths, which double as biology misconceptions, and use appropriate sources to share the "truth" about the myths. This learner-centered activity is a fun…

Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II.

Science.gov (United States)

Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Ouvry, Gilles; Perrey, David; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

2008-06-01

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

Efficiency of biological activator formulated material (BAFM) for volatile organic compounds removal--preliminary batch culture tests with activated sludge.

Science.gov (United States)

Corre, Charline; Couriol, Catherine; Amrane, Abdeltif; Dumont, Eric; Andrès, Yves; Le Cloirec, Pierre

2012-01-01

During biological degradation, such as biofiltration of air loaded with volatile organic compounds, the pollutant is passed through a bed packed with a solid medium acting as a biofilm support. To improve microorganism nutritional equilibrium and hence to enhance the purification capacities, a Biological Activator Formulated Material (BAFM) was developed, which is a mixture of solid nutrients dissolving slowly in a liquid phase. This solid was previously validated on mineral pollutants: ammonia and hydrogen sulphide. To evaluate the efficiency of such a material for biodegradation of some organic compounds, a simple experiment using an activated sludge batch reactor was carried out. The pollutants (sodium benzoate, phenol, p-nitrophenol and 2-4-dichlorophenol) were in the concentration range 100 to 1200 mg L(-1). The positive impact of the formulated material was shown. The improvement of the degradation rates was in the range 10-30%. This was the consequence of the low dissolution of the nutrients incorporated during material formulation, followed by their consumption by the biomass, as shown for urea used as a nitrogen source. Owing to its twofold interest (mechanical resistance and nutritional supplementation), the Biological Activator Formulated Material seems to be a promising material. Its addition to organic or inorganic supports should be investigated to confirm its relevance for implementation in biofilters.

New enamine derivatives of lapachol and biological activity